heroin and Pain

Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) may contribute to neonatal morbidity and mortality and result in long-term neurodevelopmental sequelae. Appropriate pain and sedation management in ventilated preterm infants may decrease the risk of GMH-IVH; however, it might be associated with harms.. To summarize the evidence from systematic reviews regarding the effects and safety of pharmacological interventions related to pain and sedation management in order to prevent GMH-IVH in ventilated preterm infants.. We searched the Cochrane Library August 2022 for reviews on pharmacological interventions for pain and sedation management to prevent GMH-IVH in ventilated preterm infants (< 37 weeks' gestation). We included Cochrane Reviews assessing the following interventions administered within the first week of life: benzodiazepines, paracetamol, opioids, ibuprofen, anesthetics, barbiturates, and antiadrenergics. Primary outcomes were any GMH-IVH (aGMH-IVH), severe IVH (sIVH), all-cause neonatal death (ACND), and major neurodevelopmental disability (MND). We assessed the methodological quality of included reviews using the AMSTAR-2 tool. We used GRADE to assess the certainty of evidence.. We included seven Cochrane Reviews and one Cochrane Review protocol. The reviews on clonidine and paracetamol did not include randomized controlled trials (RCTs) matching our inclusion criteria. We included 40 RCTs (3791 infants) from reviews on paracetamol for patent ductus arteriosus (3), midazolam (3), phenobarbital (9), opioids (20), and ibuprofen (5). The quality of the included reviews was high. The certainty of the evidence was moderate to very low, because of serious imprecision and study limitations. Germinal matrix hemorrhage-intraventricular hemorrhage (any grade) Compared to placebo or no intervention, the evidence is very uncertain about the effects of paracetamol on aGMH-IVH (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.38 to 2.07; 2 RCTs, 82 infants; very low-certainty evidence); midazolam may result in little to no difference in the incidence of aGMH-IVH (RR 1.68, 95% CI 0.87 to 3.24; 3 RCTs, 122 infants; low-certainty evidence); the evidence is very uncertain about the effect of phenobarbital on aGMH-IVH (RR 0.99, 95% CI 0.83 to 1.19; 9 RCTs, 732 infants; very low-certainty evidence); opioids may result in little to no difference in aGMH-IVH (RR 0.85, 95% CI 0.65 to 1.12; 7 RCTs, 469 infants; low-certainty evidence); ibuprofen likely results in little to no difference in aGMH-IVH (RR 0.99, 95% CI 0.81 to 1.21; 4 RCTs, 759 infants; moderate-certainty evidence). Compared to ibuprofen, the evidence is very uncertain about the effects of paracetamol on aGMH-IVH (RR 1.17, 95% CI 0.31 to 4.34; 1 RCT, 30 infants; very low-certainty evidence). Compared to midazolam, morphine may result in a reduction in aGMH-IVH (RR 0.28, 95% CI 0.09 to 0.87; 1 RCT, 46 infants; low-certainty evidence). Compared to diamorphine, the evidence is very uncertain about the effect of morphine on aGMH-IVH (RR 0.65, 95% CI 0.40 to 1.07; 1 RCT, 88 infants; very low-certainty evidence). Severe intraventricular hemorrhage (grade 3 to 4) Compared to placebo or no intervention, the evidence is very uncertain about the effect of paracetamol on sIVH (RR 1.80, 95% CI 0.43 to 7.49; 2 RCTs, 82 infants; very low-certainty evidence) and of phenobarbital (grade 3 to 4) (RR 0.91, 95% CI 0.66 to 1.25; 9 RCTs, 732 infants; very low-certainty evidence); opioids may result in little to no difference in sIVH (grade 3 to 4) (RR 0.98, 95% CI 0.71 to 1.34; 6 RCTs, 1299 infants; low-certainty evidence); ibuprofen may result in little to no difference in sIVH (grade 3 to 4) (RR 0.82, 95%. None of the reported studies had an impact on aGMH-IVH, sIVH, ACND, or MND. The certainty of the evidence ranged from moderate to very low. Large RCTs of rigorous methodology are needed to achieve an optimal information size to assess the effects of pharmacological interventions for pain and sedation management for the prevention of GMH-IVH and mortality in preterm infants. Studies might compare interventions against either placebo or other drugs. Reporting of the outcome data should include the assessment of GMH-IVH and long-term neurodevelopment.

Topics: Acetaminophen; Analgesics, Opioid; Cerebral Hemorrhage; Female; Heroin; Humans; Ibuprofen; Infant, Newborn; Infant, Premature; Midazolam; Pain; Perinatal Death; Phenobarbital; Respiration, Artificial; Systematic Reviews as Topic

Stories abound about the medical abuses that have come to define medicine and the "pseudo"-neurosciences in the Third Reich. Well known are the Nazi program of euthanasia and the neuroscientific publications that arose from it. Nevertheless, during this widespread perversion of medical practice and science, true medical heroics persisted, even in the concentration camps. In December 1942, inmates of Camp Vapniarka began experiencing painful lower extremity muscle cramps, spastic paraparesis, and urinary incontinence. In order to reduce the cost of feeding the 1200, mostly Jewish, inmates of Camp Vapniarka and surreptitiously hasten their deaths, the Nazi-affiliated Romanian officers of the camp had begun feeding them a diet high in Lathyrus sativus. L. sativus is the neurotoxin implicated in neurolathyrism, a degenerative disease of the upper motor neurons. Dr. Arthur Kessler, one of the camp's prisoners, eventually identified the source of the epidemic. Armed with this knowledge, the inmates collectively organized to halt its spread.

Topics: Concentration Camps; Heroin; History, 20th Century; Humans; National Socialism; Neurosciences; Pain

Opioids are important, if not essential, agents in treating certain types of chronic pain. However, the prevalence of drug misuse, abuse, and addiction has fostered considerable consternation among physicians, who may hesitate to prescribe these medications both due to concern for patients (misuse, abuse, and addiction), and fears of prosecution and/or professional sanction. Such practice may reflect 1) inadequate knowledge about patients' susceptibility to, or current drug misuse or abuse; 2) lack of familiarity with extant assessments and/or regulations, and/or 3) an unanticipated reaction to existing guidelines, policies or laws. We posit that assessing patients' predisposition to, and patterns of, drug misuse/abuse is a vital first step toward establishing and maintaining the safe and effective use of opioid analgesics in the treatment of chronic pain. Adherence monitoring is critical to identify patients' prior and current drug use, establish treatment basis, and evaluate compliance, so as to avoid misuse and abuse, and ensure sound and proper pain management. This paper provides a review of the numerous monitoring approaches that have been described in the literature and addresses the benefits and limitations of these techniques and tools. The complex nature of the problem of drug misuse and abuse is discussed, and while no single monitoring technique can fully address this complex issue, we describe how multiple approaches to adherence monitoring may be employed to sustain the prudent use of opioids for the treatment of chronic pain.

Topics: Analgesics, Opioid; Chronic Disease; Codeine; Drug Monitoring; Heroin; Humans; Hydrocodone; Pain; Patient Compliance

Intranasal drug administration is an easy, well-tolerated, noninvasive transmucosal route that avoids first-pass metabolism in the liver. The nasal mucosa provides an extensive, highly vascularized surface of pseudostratified ciliated epithelium. It secretes mucus that is subjected to mucociliary movement that can affect the time of contact between the drug and the surface. Absorption is influenced by anatomical and physiological factors as well as by properties of the drug and the delivery system. We review the literature on intranasal administration of fentanyl, meperidine, diamorphine, and butorphanol to treat acute pain. The adverse systemic effects are similar to those described for intravenous administration, the most common being drowsiness, nausea, and vomiting. Local effects reported are a burning sensation with meperidine and a bad taste.

Topics: Absorption; Acute Disease; Administration, Intranasal; Adult; Analgesia, Patient-Controlled; Analgesics, Opioid; Butorphanol; Child; Cross-Over Studies; Fentanyl; Heroin; Humans; Meperidine; Nasal Mucosa; Pain; Pain, Postoperative; Randomized Controlled Trials as Topic

In some countries, heroin is widely used as an analgesic agent.. The literature describing the history, pharmacology and analgesic use of heroin was reviewed.. Heroin is a semi-synthetic morphine derivative. A century ago it was considered a panacea with numerous indications. Today it is best known as a drug of abuse, but is still in use as an analgesic. Most studies that compare heroin with other analgesics have methodological shortcomings; however, they generally indicate that heroin has a clinical effect not very different from morphine. An better aqueous solubility as compared to morphine may in some situations be advantageous. Because of a proposed incomplete cross-tolerance between heroin and other opioid analgesics, it may be used if the patient shows sub-therapeutic response to first-line opioids.. Although not well documented, heroin appears to be an effective analgesic with certain properties different from those of morphine. It may be of clinical value in conditions with acute and/or terminal pain.

Topics: Adult; Analgesia, Obstetrical; Analgesics, Opioid; Child; Female; Heroin; Humans; Pain; Pain, Postoperative; Pregnancy; Terminal Care

This, the last article in the series, describes the administration of analgesics other than via the enteral route in the treatment of chronic severe pain.

Topics: Administration, Cutaneous; Analgesics; Chronic Disease; Fentanyl; Heroin; Humans; Infusions, Parenteral; Injections, Subcutaneous; Pain

Topics: Heroin; Humans; Hydromorphone; Infusion Pumps; Morphine; Narcotics; Neoplasms; Pain

Heroin is currently being advocated by some as a superior therapeutic agent for use in terminal illness. However, a review of the literature on heroin presently available does not support this contention. Administered orally, heroin is approximately 1.5 times more potent than morphine in controlling chronic pain in terminal cancer patients. Its effects on mood and the incidence and nature of side effects do not differ from those of morphine except in males where poorer pain control probably accounts for the worse effect on mood. Given parenterally for acute pain, heroin is 2-4 times more potent than morphine and faster in onset of action. When the potency difference is accounted for, the pharmacological effects of heroin do not differ appreciably from those of morphine. Heroin is metabolized to 6-acetylmorphine and morphine. After oral administration of heroin, morphine but not heroin or 6-acetylmorphine is detected in blood. In this case, heroin is a prodrug for the delivery of systemic morphine. Following acute i.v. administration, heroin appears transiently in blood with a half-life of about 3 min. The half-life of heroin exposed to blood or serum in vitro is 9-22 min, indicating that organ metabolism is involved in blood clearance as well. Direct renal clearance of heroin is less than 1% of the administered dose. In animal studies, heroin and 6-acetylmorphine are both more potent and faster acting than morphine as analgesics, effects attributed to their greater lipid solubility and subsequent penetration of the blood-brain barrier. Given centrally, morphine is more potent than heroin and 6-acetylmorphine in producing analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analgesia; Animals; Brain; Codeine; Depression; Euphoria; Female; Half-Life; Heroin; Humans; Hydromorphone; Kinetics; Liver; Male; Morphine; Morphine Derivatives; Neoplasms; Pain; Sex Factors; Solubility; Terminal Care; Water

Topics: Analgesia; Analgesics; Animals; Blood Pressure; Cyclizine; Heart Arrest; Heroin; Humans; Injections, Intravenous; Methadone; Morphine; Myocardial Infarction; Nausea; Pain; Pentazocine; Pulmonary Circulation; Respiration; Shock, Cardiogenic; Spirometry; Vomiting

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Biphenyl Compounds; Chemistry, Pharmaceutical; Heroin; Morphine; Nalorphine; Pain; Piperidines

Ibudilast, a nonselective phosphodiesterase inhibitor, is used clinically in Asia for the treatment of asthma and poststroke dizziness. Recent preclinical studies have suggested that it also inhibits glial cell activation in rodents, and may alter opioid-mediated effects, including analgesia and withdrawal symptoms. The effects of ibudilast on the abuse potential of opioids in humans are largely unknown. The present study was designed to examine the influence of ibudilast on subjective (including drug craving), reinforcing, and analgesic effects of oxycodone in human volunteers diagnosed with opioid dependence (equivalent to moderate-severe opioid use disorder). Non-treatment-seeking opioid-dependent male volunteers (n=11) underwent an in-patient detoxification with morphine, followed by maintenance on placebo (0 mg b.i.d.) and active ibudilast (50 mg b.i.d.). Under each maintenance dose, six experimental sample and choice sessions were completed involving oral oxycodone administration (0, 15, and 30 mg/70 kg, p.o.). Subjective effects of oxycodone and drug craving were measured with visual analog scales (VAS) and a Drug Effects Questionnaire. The cold pressor test was used to produce pain, and a modified progressive-ratio choice procedure was used to measure the reinforcing effects of oxycodone. Under the active ibudilast condition compared with the placebo condition, ratings of drug liking following 15 mg of oxycodone were decreased significantly. The mean drug breakpoint value was also significantly lower in the active vs the placebo ibudilast condition under the 15 mg oxycodone condition, but not significantly lower under the 30 mg oxycodone condition. Heroin craving was significantly reduced under active ibudilast vs placebo, and similar effects were observed for tobacco and cocaine craving. Furthermore, mean subjective ratings of pain were lower in the active ibudilast condition. Our data suggest that ibudilast may be useful for treating opioid use disorders and it may enhance the analgesic effects of oxycodone.

Topics: Analgesics, Opioid; Craving; Heroin; Humans; Male; Middle Aged; Morphine; Opioid-Related Disorders; Oxycodone; Pain; Phosphodiesterase Inhibitors; Pyridines

The painful crisis is the commonest acute presentation of sickle cell disease (SCD), yet effective pain control in hospital is often delayed, inadequate and dependent on injected opiates. Intranasal diamorphine (IND) has been used in paediatric emergency departments for management of acute pain associated with fractures, but the analgesic effect is short lived. We evaluated its efficacy and safety when given in combination with intravenous or oral morphine for rapid analgesia for children presenting to our emergency department with painful crisis of SCD. In phase 1, nine patients received IND plus intravenous morphine. In phase 2, 13 received IND plus oral morphine. There was a rapid improvement in pain score; the proportions in severe pain at t = 0, 15, 30 and 120 minutes in phase 1 were 78%, 11%, 0% and 11%, respectively; in phase 2, 77%, 30%, 15% and 0%, respectively. There were no serious side effects and questionnaire scores indicated that children found IND effective and acceptable. IND can be recommended for acute control of sickle pain in children presenting to hospital.

Topics: Acute Disease; Administration, Intranasal; Administration, Oral; Adolescent; Analgesics, Opioid; Anemia, Sickle Cell; Child; Child, Preschool; Drug Therapy, Combination; Emergency Service, Hospital; Heroin; Humans; Infant; Infusions, Intravenous; Injections, Intravenous; Morphine; Pain; Pain Measurement

Current best practice for treating acute severe pain in children is to administer intravenous or intranasal opioid. Intranasal diamorphine offers less traumatic analgesia than the potentially difficult and distressing intravenous route. However, there has been no direct comparison of intranasal and intravenous diamorphine nor are there pharmacokinetic data for intranasal diamorphine in children.. To compare plasma morphine concentration-time profiles following intranasal and intravenous diamorphine administration.. Observational.. A&E department in a city-centre paediatric teaching hospital.. Children, aged 3-13 years, with isolated limb fracture.. An intravenous catheter was sited and baseline blood taken. The first 12 children received intravenous diamorphine (0.1 mg/kg), and the subsequent 12 intranasal diamorphine (0.1 mg/kg) in 0.2 ml sterile water drops. Subsequent samples were taken at 2, 5, 10, 20, 30 and 60 min.. Plasma morphine radioimmunoassay.. Peak plasma morphine concentrations were higher (median 109 vs 36 nmol/l), and occurred earlier (median 2 vs 10 min), with greater area under the curve (3761 vs 1794 nmol/l/h) following intravenous compared to intranasal diamorphine (all p<0.001, Mann-Whitney U test). Higher plasma concentrations at 60 min (47 vs 32 nmol/l) were also observed following intravenous diamorphine (p = 0.01, Mann-Whitney U test).. Our evidence supports the wider use of diamorphine administration by nasal drops in children, as it shows that adequate plasma levels of morphine are usually achieved. However, we demonstrated significantly attenuated and delayed peak plasma morphine levels with lower levels at 1 h with intranasal compared with intravenous diamorphine.

Topics: Administration, Intranasal; Adolescent; Analgesics, Opioid; Child; Child, Preschool; Drug Administration Schedule; Emergency Service, Hospital; Female; Fractures, Bone; Heroin; Humans; Injections, Intravenous; Male; Morphine; Pain; Time Factors

To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour.. Randomised controlled trial.. The South Glasgow University Hospitals NHS Trust.. Primigravidae and multigravidae in labour at term (37-42 weeks).. Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks.. Analgesia requirements during labour and women's satisfaction with the method of pain relief.. Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS.. Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.

Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Female; Gravidity; Heroin; Humans; Infant, Newborn; Injections, Intramuscular; Obstetric Labor Complications; Pain; Patient Satisfaction; Pregnancy; Pregnancy Outcome

Topics: Aged; Aged, 80 and over; Analgesics, Opioid; Bandages; Drug Combinations; Female; Heroin; Humans; Hydrogels; Male; Middle Aged; Pain; Pressure Ulcer; Retrospective Studies; Treatment Outcome

Pressure ulcer pain, a common problem among palliative care patients, does not respond well to oral analgesics. There have been case reports in the medical literature describing the successful use of topical opioids for painful skin conditions. So far, these topical opioids have not been compared to placebo. To determine the effectiveness of diamorphine gel to control pressure ulcer pain and compare it with placebo, a randomized, double blind, placebo-controlled crossover trial was conducted in 13 patients with painful grade II or III pressure ulcers. Patients resided on the inpatient unit at St. Christopher's Hospice, London, UK. Seven patients completed the study and provided pain scores before and after diamorphine or placebo gel application. Pain scores improved significantly after diamorphine gel application compared with placebo (P<0.05). Diamorphine gel appears to be an effective treatment for pain caused by stage II or III pressure ulcers. It is probably as safe as placebo in regards to side effects, but a larger study would be required to confirm these results.

Topics: Administration, Topical; Aged; Aged, 80 and over; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Female; Gels; Heroin; Humans; Male; Middle Aged; Pain; Pain Measurement; Pilot Projects; Pressure Ulcer

To compare the effectiveness of nasal diamorphine spray with intramuscular morphine for analgesia in children and teenagers with acute pain due to a clinical fracture, and to describe the safety profile of the spray.. Multicentre randomised controlled trial.. Emergency departments in eight UK hospitals.. Patients aged between 3 and 16 years presenting with a clinical fracture of an upper or lower limb.. Patients' reported pain using the Wong Baker face pain scale, ratings of reaction to treatment of the patients and acceptability of treatment by staff and parents, and adverse events.. 404 eligible patients completed the trial (204 patients given nasal diamorphine spray and 200 given intramuscular morphine). Onset of pain relief was faster in the spray group than in the intramuscular group, with lower pain scores in the spray group at 5, 10, and 20 minutes after treatment but no difference between the groups after 30 minutes. 80% of patients given the spray showed no obvious discomfort compared with 9% given intramuscular morphine (difference 71%, 95% confidence interval 65% to 78%). Treatment administration was judged acceptable by staff and parents, respectively, for 98% (199 of 203) and 97% (186 of 192) of patients in the spray group compared with 32% (64 of 199) and 72% (142 of 197) in the intramuscular group. No serious adverse events occurred in the spray group, and the frequencies of all adverse events were similar in both groups (spray 24.1% v intramuscular morphine 18.5%; difference 5.6%, -2.3% to 13.6%).. Nasal diamorphine spray should be the preferred method of pain relief in children and teenagers presenting to emergency departments in acute pain with clinical fractures. The diamorphine spray should be used in place of intramuscular morphine.

Topics: Administration, Intranasal; Adolescent; Analgesics, Opioid; Child; Child, Preschool; Emergencies; Female; Fractures, Bone; Heroin; Humans; Injections, Intramuscular; Male; Morphine; Pain; Pain Measurement; Patient Satisfaction; Time Factors

To compare the pain relief and side effects of intramuscular pethidine with intramuscular diamorphine in labour.. Double-blind randomised controlled trial.. The labour ward in a UK teaching hospital.. Sixty-nine nulliparous women and 64 multiparous women in labour who requested narcotic analgesia and remained undelivered one hour after trial entry.. Nulliparous women were randomised to receive either 150 mg intramuscular pethidine or 7.5 mg intramuscular diamorphine. Multiparous women were randomised to receive either 100 mg intramuscular pethidine or 5 mg intramuscular diamorphine. All participants received the anti-emetic prochloroperazine at the same time as the trial drugs.. Maternal analgesia assessed by a visual analogue score and verbal scales of pain intensity and pain relief, maternal sedation and vomiting, neonatal outcome assessed by Apgar scores and the need for resuscitation.. More women allocated to receiving pethidine than to diamorphine reported slight or no pain relief at 60 minutes after administration of these drugs (P = 0.03). This trend was repeated in most of the other measures for maternal analgesia. There was no difference in maternal sedation, but the incidence of vomiting within 60 minutes was lower for women who received diamorphine (P = 0.02). Pethidine was associated with lower Apgar scores at 1 minute (P < 0.05).. Intramuscular diamorphine in labour appears to have some benefits, compared with intramuscular pethidine, but the trial was small and further research, particularly into alternative opioids and long term effects on the infants is still needed.

Topics: Analgesics, Opioid; Double-Blind Method; Female; Heroin; Humans; Injections, Intramuscular; Meperidine; Obstetric Labor Complications; Pain; Parity; Pregnancy; Pregnancy Outcome

Mucositis remains an important problem following BMT and may delay discharge from hospital. Patient-controlled analgesia (PCA) systems have been reported to be of benefit in controlling BMT-associated mucositis. The present study comprised 65 patients (age range 16-68 years; 19 allografts, 29 peripheral blood stem cell autografts and 17 autologous bone marrow). Subjects were prospectively randomised to receive intravenous diamorphine for pain relief either by conventional continuous infusion (CI) or by PCA, using a Medex Walkman 440 delivery system. Each patient assessed his/her pain control and nausea daily by a visual analogue scale. Twenty-two patients did not require any diamorphine. Four patients required diamorphine for pain other than mucositis, and four patients failed PCA control. Of 35 assessable cases, no difference in pain control was noted between CI and PCA. However, PCA-controlled patients required significantly less diamorphine than CI controlled patients (mean, 131 +/- 23 mg for PCA vs 296 +/- 40 mg for CI; P = 0.001), and PCA required fewer days of diamorphine than CI (mean, 7.17 +/- 0.66 days for PCA, 9.00 +/- 0.65 days for CI; P = 0.03). Side-effects were minimal and equivalent in the two arms. The findings suggest that PCA and CI offer equivalent control of the pain of BMT-associated mucositis, but PCA requires less total consumption and duration of diamorphine therapy.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Bone Marrow Transplantation; Female; Heroin; Humans; Infusions, Intravenous; Male; Middle Aged; Mouth Mucosa; Pain; Stomatitis; Transplantation, Autologous; Transplantation, Homologous

To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial.. Fifty or 200 mcg/kg were infused intravenously over 30 minutes, followed by a 15 mcg/kg/hour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones.. Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found.. Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcg/kg loading dose seems to be safe and effective.

Topics: Analgesics, Opioid; Blood Pressure; Double-Blind Method; Drug Administration Schedule; Heroin; Humans; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Pain; Respiration; Respiration, Artificial

In a randomly allocated double blind study of 54 primigravidae, we examined the relative efficacy of the addition of diamorphine 3 mg to either an initial bolus or an infusion of bupivacaine. Both groups received an initial bolus of 10 ml of bupivacaine 0.25% followed by an infusion of bupivacaine 0.1% at 10 ml.h-1. Group 1 received diamorphine 3 mg in the bolus and group 2 received diamorphine 3 mg in the initial 100 ml of infusion solution. Both groups had comparable total bupivacaine requirements. Analgesia, assessed by visual analogue scores, was superior at 7h in group 2, but was similar at all other times. Sedation scores were significantly lower in group 2 for the first 3h and the incidence of nausea was significantly lower in group 2. The addition of diamorphine, whether as a bolus or added to an infusion of bupivacaine, results in similar quality of analgesia, but there is a reduction in side effects when diamorphine is administered in an infusion.

Topics: Adult; Analgesia, Epidural; Analgesia, Obstetrical; Bupivacaine; Conscious Sedation; Double-Blind Method; Drug Combinations; Female; Heroin; Humans; Infusions, Parenteral; Injections, Epidural; Pain; Pregnancy

We performed a combined analysis of the results from four controlled single-dose relative-potency studies to assess the impact of inferred pain mechanism on the response to an opioid drug. A total of 168 patients received 474 administrations of either morphine or heroin, and we assessed the analgesic response during a 6-hour period with visual analog scales. We summarized this as a total pain relief (TOTPAR) score. Two experienced pain clinicians reviewed information about pain characteristics and designated each case according to the inferred pain mechanism (neuropathic, nociceptive, or mixed) and the degree of confidence in the inferred mechanism (definite versus probable/possible). They grouped the cases as follows: nociceptive pain only (n = 205), neuropathic pain only (n = 49), and mixed (n = 220). We compared pain relief achieved by patients with different mechanisms, with TOTPAR adjusted for significant covariates (duration of prior opioid administration, doses of opioid administered in the previous 48 hours, pain intensity at the start of the study, BUN:creatinine ratio, and dose of administered opioid). The adjusted mean TOTPAR score of the group with any neuropathic pain was significantly lower than that of the group with nociceptive pain only (26.1 versus 20.4, p = 0.02). The score of the group with definite nociceptive pain alone (adjusted mean TOTPAR = 28.0) was significantly higher than scores of the groups with possible/probable nociceptive pain (TOTPAR = 19.9), mixed mechanisms (TOTPAR = 20.2), definite neuropathic pain alone (TOTPAR = 20.6), and possible/probable neuropathic pain alone (TOTPAR = 22.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Female; Heroin; Humans; Male; Middle Aged; Morphine; Neoplasms; Nervous System Diseases; Nociceptors; Pain; Pain Measurement; Palliative Care

A questionnaire study was carried out to investigate the needs of women undergoing a medical abortion induced by mifepristone in combination with either gemeprost pessaries or oral misoprostol. One-hundred-and-eighty women undergoing medical abortion of pregnancy of up to 63 days amenorrhoea were randomised to treatment in the sitting-room (treatment room) or in the ward. Overall, 77% and 69% treated in the sitting-room and ward, respectively, would have preferred treatment in the sitting-room. Fifty-four per cent did not wish their partner or friend to be present and 76% would prefer to stay in hospital following administration of prostaglandin. Ninety-five per cent of the patients would recommend this method of abortion to their friends. Women who received misoprostol required significantly less analgesia than women who were given 1 mg gemeprost as a vaginal pessary. The requirement for opiate analgesia was not influenced by parity, gestation of pregnancy, history of dysmenorrhoea or the dose of mifepristone. Almost 100% of the patients were satisfied with this method of treatment. This study indicates that the majority of women undergoing medical abortion prefer to be treated in a group, a method which is highly cost-effective.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Acetaminophen; Administration, Oral; Adolescent; Adult; Alprostadil; Bias; Codeine; Female; Heroin; Humans; Mifepristone; Misoprostol; Pain; Patient Satisfaction; Pessaries; Pregnancy

In a random, double-blind crossover trial using an ischaemic limb pain model we have assessed the speed of onset of analgesia after an i.v. bolus of equipotent doses of diamorphine and morphine in 12 healthy male volunteers. Pain and its subsequent relief were assessed by means of a visual analogue scale. Two of the subjects found diamorphine acted quicker than morphine, one found no difference and nine found that morphine was quicker than diamorphine. The mean time to diamorphine effect was 53% greater than for morphine (P less than 0.005, Wilcoxon rank sum test). These findings suggest that, for rapid relief of pain, morphine is more suitable than diamorphine.

Topics: Adult; Arm; Double-Blind Method; Heroin; Humans; Injections, Intravenous; Ischemia; Male; Models, Biological; Morphine; Pain; Pain Measurement; Time Factors

A double-blind study comparing placebo and haem arginate was conducted in 12 patients with acute intermittent porphyria. 2 days after admission in attack patients were randomised to receive intravenous haem arginate 3 mg/kg per 24 h for 4 days or placebo. 9 patients were readmitted with a further attack and were given the alternative treatment. Before randomisation the paired attacks were of similar severity with respect to urinary porphobilinogen (PBG) excretion and clinical manifestations. With haem arginate the median PBG excretion of the 9 patients with two attacks (normal range 0-16 mumol per 24 h) fell significantly from 332 mumol per 24 h (range 137-722) on admission to a median lowest level of 40 (range 22-105). On placebo, median PBG excretion was 382 (range 196-542) on admission, falling to 235 (range 128-427). Median duration of admission after the start of treatment was 11 days (range 2-28) for placebo and 8 days (3-26) for haem arginate. Median total analgesic requirement between the start of treatment and discharge was 8150 mg pethidine equivalents (range 0-17,650) with placebo versus 6425 (range 50-20,650) with haem arginate. Phlebitis occurred in 5 patients on haem arginate and in 2 on placebo. Haem arginate effectively reduces porphyrin precursor overproduction in the acute porphyric attack but this reduction is not accompanied by striking resolution of the clinical manifestations of the attack.

Topics: Acute Disease; Adolescent; Arginine; Clinical Trials as Topic; Double-Blind Method; Female; Heme; Heroin; Humans; Infusions, Intravenous; Injections, Intravenous; Liver Diseases; Male; Meperidine; Pain; Phlebitis; Porphyrias; Random Allocation; Recurrence; Severity of Illness Index

Measurement of pain in cancer patients requires all the procedural safeguards essential for the measurement of subjective responses, including the employment of active and inactive controls, double-blind techniques, randomization, and statistical verification of results. Pain is traditionally measured in analgesic studies by employing verbal descriptors of intensity, but more recently visual analogues of pain intensity have been used and generally provide more sensitive measures of pain intensity. Patients with chronic pain tend to rate the categories representing more intense pain as lower in the visual analogue scale than do patients with postoperative pain. This may well reflect differences in the prior pain experiences of the two groups. Patients with chronic cancer pain have greater positive mood effects after the narcotic, morphine, than after the non-steroidal antiinflammatory analgesic, zomepirac, and this appears to be independent of analgesic activity. It is possible to design crossover analgesic studies in cancer patients so as to minimize carry-over effects, and such studies are more efficient than parallel group assays. Crossover studies also provide the ability to measure carry-over when it occurs.

Topics: Analgesia; Analgesics; Clinical Trials as Topic; Emotions; Heroin; Humans; Methods; Morphine; Neoplasms; Pain; Research Design; Surveys and Questionnaires; Tolmetin

Topics: Clinical Trials as Topic; Heroin; Humans; Legislation, Drug; Morphine; Pain; United States

Topics: Chronic Disease; Clinical Trials as Topic; Female; Heroin; Humans; Legislation, Drug; Male; Morphine; Pain; Sex Factors; United States

1. A method is described for comparing narcotic analgesics and adjuvants in patients with terminal cancer. 2. A randomized controlled trial of orally administered diamorphine and morphine is reported to illustrate the method. 3. It is concluded that there is no over-all clinical difference between diamorphine and morphine when administered by mouth every four hours at individually optimized doses in association with cocaine and a phenothiazine. 4. The validity, reliability and sensitivity of the method are discussed.

Topics: Aged; Analgesics, Opioid; Clinical Trials as Topic; Drug Evaluation; Female; Heroin; Humans; Male; Methods; Morphine; Neoplasms; Pain; Palliative Care; Surveys and Questionnaires; Terminal Care

Topics: Administration, Oral; Adult; Aged; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Tolerance; Female; Heroin; Humans; Infusions, Parenteral; Male; Middle Aged; Morphinans; Neoplasms; Pain; Substance-Related Disorders; Terminal Care; Time Factors

Topics: Affect; Benperidol; Clinical Trials as Topic; Diazepam; Drug Synergism; Female; Fentanyl; Heroin; Humans; Morphine; Neuroleptanalgesia; Pain; Perception; Phenoperidine; Placebos; Pressure; Tibia

Topics: Acute Disease; Adult; Aged; Blood Pressure; Clinical Trials as Topic; Female; Heart Rate; Heroin; Humans; Injections, Intravenous; Male; Methadone; Middle Aged; Morphine; Myocardial Infarction; Pain; Pentazocine; Respiration

The brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-based

Topics: Analgesics, Opioid; Animals; Female; Heroin; Heroin Dependence; Male; Nucleus Accumbens; Pain; Rats; Rats, Transgenic; Receptors, Opioid; Receptors, Opioid, mu

Medications for opioid use disorder (MOUD; methadone, buprenorphine, naltrexone) are the most effective treatments for OUD, and MOUD is protective against fatal overdoses. However, continued illegal drug use can increase the risk of treatment discontinuation. Given the widespread presence of fentanyl in the drug supply, research is needed to understand who is at greatest risk for concurrent MOUD and drug use and the contexts shaping use and treatment discontinuation.. From 2017 to 2020, Massachusetts residents with past-30-day illegal drug use completed surveys (N = 284) and interviews (N = 99) about MOUD and drug use. An age-adjusted multinomial logistic regression model tested associations between past-30-day drug use and MOUD use (current/past/never). Among those on methadone or buprenorphine (N = 108), multivariable logistic regression models examined the association between socio-demographics, MOUD type; and past-30-day use of heroin/fentanyl; crack; benzodiazepines; and pain medications. Qualitative interviews explored drivers of concurrent drug and MOUD use.. Most (79.9%) participants had used MOUD (38.7% currently; 41.2% past), and past 30-day drug use was high: 74.4% heroin/fentanyl; 51.4% crack cocaine; 31.3% benzodiazepines, and 18% pain medications. In exploring drug use by MOUD history, multinomial regression analyses found that crack use was positively associated with past and current MOUD use (outcome referent: never used MOUD); whereas benzodiazepine use was not associated with past MOUD use but was positively associated with current use. Conversely, pain medication use was associated with reduced odds of past and current MOUD use. Among those on methadone or buprenorphine, separate multivariable logistic regression models found that benzodiazepine and methadone use were positively associated with heroin/fentanyl use; living in a medium-sized city and sex work were positively associated with crack use; heroin/fentanyl use was positively associated with benzodiazepine use; and witnessing an overdose was inversely associated with pain medication use. Many participants qualitatively reported reducing illegal opioid use while on MOUD, yet inadequate dosage, trauma, psychological cravings, and environmental triggers drove their continued drug use, which increased their risk of treatment discontinuation and overdose.. Findings highlight variations in continued drug use by MOUD use history, reasons for concurrent use, and implications for MOUD treatment delivery and continuity.

Topics: Analgesics, Opioid; Benzodiazepines; Buprenorphine; Crack Cocaine; Drug Overdose; Fentanyl; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Pharmaceutical Preparations

Diamorphine is a strong opioid licensed in the UK for many uses, including moderate and severe pain. In the early 2000s, its use in palliative medicine was widespread before a supply disruption led to preferential use of alternative, cheaper opioids. Though these supply issues were resolved, the use of diamorphine in palliative medicine has remained reduced, particularly with another UK supply disruption in 2021. Following anecdotal reports of good results from diamorphine use in younger patients, this piece discusses two cases of young patients with metastatic cancers suffering significant pain and psychological distress. Both patients were approaching end of life and required high doses of opioids, benzodiazepines and co-analgesics, all given to limited benefit. Both patients were rotated to diamorphine giving objective and subjective improvement in symptoms. These cases are presented in the context of newer information and description of the biochemical actions of diamorphine and its metabolites, which exert their own clinical effect before themselves generating active metabolites. Various trials on, and discussion about, diamorphine's unique metabolism and subsequent central nervous system effects help argue for its use in situations where extreme pain and psychological distress overlap.

Topics: Analgesics, Opioid; Heroin; Humans; Neoplasms; Pain

Opioids and benzodiazepines are cornerstones of the pharmacological management of pain and agitation in palliative medicine. Oral drug delivery is the most popular route of administration, with the subcutaneous route typically utilized where oral medications are not tolerated or are ineffective. Intranasal drug delivery offers an important alternative administration route, with benefits including ease of administration, tolerability and avoidance of needle use, and is particularly useful in the community, where medications may be administered by lay carers or by patients themselves. Intranasal diamorphine and intranasal midazolam both have demonstrated efficacy and safety in adult and pediatric cohorts, however there is limited research into their use in managing pain and agitation in palliative care. We describe the management of three patients under the community palliative care team who received intranasal diamorphine, two of whom also received intranasal midazolam, to manage breakthrough symptoms of pain and agitation at home. In each case, the patient or their relative was taught how to prepare and administer the relevant intranasal medication. This case series demonstrates that for selected patients, diamorphine and midazolam administered intranasally by patients or lay carers at home is efficacious, acceptable and generally well tolerated.

Topics: Administration, Intranasal; Adult; Child; Heroin; Humans; Midazolam; Pain; Palliative Care

Necrotizing soft tissue infection (NSTI) is rare and characterized by rapid onset and spread of inflammation and necrosis. The infection starts within the fascia but can rapidly progress to include musculature, subcutaneous fat, and overlying skin. Its presentation is considered a surgical emergency. Persons who use intravenous or subcutaneous opioids are at higher risk of NSTIs.. The purpose of this case report is to describe the positive clinical outcome after consulting with wound specialists and using a dressing regimen to expedite more rapid wound healing, shortened time to skin graft, and improved pain tolerance in a patient with a history of intravenous and subcutaneous heroin use.. The patient presented with an NSTI that required extensive debridement of the bilateral upper extremities. The acute surgical wound service was consulted. A dressing regimen consisting of hypochlorous acid-preserved wound cleansing, followed by carboxymethylcellulose fiber with 1.2% ionic silver covered by hydrocellular foam to promote a moist healing environment, was used to facilitate granulation.. Healthy granulation tissue was noted 6 days after debridement. The improved rate of granulation and the patient's tolerance to dressing changes secondary to decreased pain from these dressings significantly expedited the time to graft and wound healing. The patient underwent split-thickness skin grafting 10 days after debridement. There was 100% uptake of the grafts on postgraft day 8.. The favorable clinical outcome suggests that early consultation with wound specialists and implementation of the dressing regimen were effective in this patient regarding improved pain control and healing. However, because the patient left against medical advice on hospital day 20, the clinical course could not be followed beyond the first few postoperative weeks.

Topics: Bandages; Forearm; Heroin; Humans; Pain; Skin Transplantation; Soft Tissue Infections

Polysubstance use among people who misuse opioids (PWMO) is highly prevalent, but understudied. We defined, estimated, and analyzed national polysubstance use patterns among PWMO using National Household Survey on Drug Use and Health data (2017-2019).. We obtained estimates of past-month patterns of polydrug use using cluster analysis and latent class/profile analysis. We considered misuse of prescription opioids and use of heroin, cocaine (including crack), marijuana, alcohol, and "other" substances.. We identified a five-cluster solution for binary indicators of past-month use and a six-cluster solution for frequency of use. The largest binary cluster (37%) included misuse of prescription opioids and use of alcohol. The second-largest cluster (15%) included misuse of prescription opioids, alcohol, marijuana, and "other" substances. Among those who used heroin, 36% used methamphetamine. In terms of frequency of use, the largest cluster among people who misuse opioid who used multiple substances (almost 40%) misused prescription pain relievers, alcohol, and marijuana infrequently. The second-largest cluster (23%) used marijuana almost daily and misused prescription pain relievers an average of 6.6 days. PWMO in a cluster of almost daily heroin use indicated use of methamphetamine, marijuana, and prescription opioids. Those who used methamphetamine, were using it more than 15 days a month.. We have developed reference measures of polydrug patterns among US household population and estimated their demographic characteristics. We identified clusters of high-risk polydrug use. These findings have implications for the development of prevention and treatment solutions in the United States.

Topics: Analgesics, Opioid; Heroin; Humans; Methamphetamine; Opioid-Related Disorders; Pain; Prescription Drug Misuse; Prescriptions; Substance-Related Disorders; United States

In this paper, I propose a life cycle model of painkiller consumption that combines the theory of health deficit accumulation with the theory of addiction. Chronic pain is conceptualized as a persistent negative shock to lifetime utility that can be treated by pain relief medication. Individuals treated with opioid pain relievers (OPR) develop addiction, which increases their demand for opioids and reduces their welfare and life expectancy through side effects and potential overdose. I calibrate the model for a benchmark American and investigate the comparative dynamics of alternative drug characteristics, pain intensities, and ages of onsets of pain as well as their implications for welfare and life expectancy. Computational experiments are used to identify fully rational and imperfectly rational addiction behavior. Fully rational addicts reduce OPR use when new information about the addictive potential of these drugs arrives. Imperfectly rational addicts further develop their addiction and switch to illicit opioid use. Likewise, a discontinued prescription helps fully rational addicts to quit quickly, while it induces imperfectly rational individuals to take up heroin. I also discuss treatment of OPR addiction and the use of opioids in palliative care.

Topics: Analgesics, Opioid; Heroin; Humans; Longevity; Opioid-Related Disorders; Pain; United States

Estimates from the National Survey on Drug Use and Health (Substance Abuse and Mental Health Services Administration [SAMHSA], 2019) suggest 3.6% of persons aged 12 and older misused prescription pain relievers in the past year and 0.3% used heroin. However, research suggests that most individuals drastically overestimate rates of substance use and misuse. Those who overestimate substance misuse are often more likely to misuse substances themselves (Kilmer et al., 2015; McCabe, 2008).

Topics: Adult; Analgesics, Opioid; Female; Heroin; Humans; Opioid-Related Disorders; Pain; Prescription Drug Misuse; Prescriptions

Opioid overdose mortality continues to increase in the United States despite significant investments to reverse the epidemic. The national response to-date has focused primarily on reducing opioid prescribing, yet reductions in prescribing have been associated with patients reporting uncontrolled pain, psychological distress, and transition to illicit substances. The aim of this study is to qualitatively explore chronic pain management experiences among PLWH with a history of illicit substance use after long-term opioid therapy reductions or discontinuations.. We analyzed 18 interviews, stopping upon reaching thematic saturation, with HIV-positive participants with a history of substance use who were enrolled in a longitudinal cohort study to assess the impact of prescribing changes among patients with chronic pain. Participants in this nested qualitative study had been reduced/discontinued from opioid pain relievers (OPRs) within the 12 months prior to interview. Interviews were audio-recorded and transcribed verbatim. Two analysts coded all interviews, interrater reliability was measured, and coding discrepancies discussed. The study took place in San Francisco, California in 2018.. Eleven participants were male with a mean age of 55; 8 were African American and 8 were White. All participants were HIV-positive, actively engaged in primary care, and had a lifetime history of illicit substance use. Twelve reported using illicit substances within the past year, including non-prescription opioids/heroin (10), and stimulant use (10). After being reduced/discontinued from their long-term opioid therapy, patients reported developing complex multimodal pain management systems that often included both nonpharmacological approaches and illicit substance use. Participants encountered a range of barriers to nonpharmacological therapies including issues related to accessibility and availability. Participants often reported attempts to replicate their prior OPR prescription by seeking out the same medication and dose from illicit sources and reported transitioning to heroin after exhausting other options.. After being reduced/discontinued from OPRs, HIV-positive patients with a history of substance use reported experimenting with a range of pain management modalities including nonpharmacological therapies and illicit substance use to manage symptoms of opioid withdrawal and pain. Providers should consider that any change to a patients' long-term opioid therapy may result in experimentation with pain management outside of the medical setting and may want to employ patient-centered, holistic approaches when managing patients' opioid prescriptions and chronic pain.

Topics: Acupuncture; Analgesics, Opioid; Drug Prescriptions; Female; Heroin; HIV Infections; Humans; Male; Middle Aged; Opioid-Related Disorders; Pain; Pain Management; San Francisco; Transgender Persons

Persistent transcriptional and morphological events in the nucleus accumbens (NAc) and other brain reward regions contribute to the long-lasting behavioral adaptations that characterize drug addiction. Opiate exposure reduces the density of dendritic spines on medium spiny neurons of the NAc; however, the underlying transcriptional and cellular events mediating this remain unknown. We show that heroin self-administration negatively regulates the actin-binding protein drebrin in the NAc. Using virus-mediated gene transfer, we show that drebrin overexpression in the NAc is sufficient to decrease drug seeking and increase dendritic spine density, whereas drebrin knockdown potentiates these effects. We demonstrate that drebrin is transcriptionally repressed by the histone modifier HDAC2, which is relieved by pharmacological inhibition of histone deacetylases. Importantly, we demonstrate that heroin-induced adaptations occur only in the D1

Topics: Animals; Behavior, Animal; Epigenesis, Genetic; Heroin; Histone Deacetylase 2; Male; Microfilament Proteins; Neuronal Plasticity; Neurons; Neuropeptides; Nucleus Accumbens; Opiate Alkaloids; Opioid-Related Disorders; Pain; Rats, Sprague-Dawley; Synapses

Topics: Analgesics, Opioid; Heroin; Humans; Pain; Palliative Care

Skin and soft tissue infections (SSTIs) are prevalent among people who inject heroin (PWIH). Delays in seeking health care lead to increased costs and potential mortality, yet the barriers to accessing care among PWIHs are poorly understood.. We administered a quantitative survey (N = 145) and conducted qualitative interviews (N = 12) with PWIH seeking syringe exchange services in two U.S. cities.. 66% of participants had experienced at least one SSTI. 38% reported waiting two weeks or more to seek care, and 57% reported leaving the hospital against medical advice. 54% reported undergoing a drainage procedure performed by a non-medical professional, and 32% reported taking antibiotics that were not prescribed to them. Two of the most common reasons for these behaviors were fear of withdrawal symptoms and inadequate pain control, and these reasons emerged as prominent themes in the qualitative findings. These issues are often predicated on previous negative experiences and exacerbated by stigma and an asymmetrical power dynamic with providers, resulting in perceived barriers to seeking and completing care for SSTIs.. For PWIH, unaddressed pain and withdrawal symptoms contribute to profoundly negative health care experiences, which then generate motivation for delaying care SSTI seeking and for discharge against medical advice. Health care providers and hospitals should develop policies to improve pain control, manage opioid withdrawal, minimize prejudice and stigma, and optimize communication with PWIH. These barriers should also be addressed by providing medical care in accessible and acceptable venues, such as safe injection facilities, street outreach, and other harm reduction venues.

Topics: Abscess; Adult; Cross-Sectional Studies; Female; Heroin; Humans; Male; Middle Aged; Pain; Pain Management; Patient Acceptance of Health Care; Prejudice; Retrospective Studies; Social Stigma; Soft Tissue Infections; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

To date there have been no studies investigating the characteristics of pain in Chinese heroin-dependent patients (HDPs) receiving methadone maintenance treatment (MMT). This study examined the frequency and socio-demographic and clinical correlates of pain in HDPs under MMT. A consecutive sample of 603 HDPs was recruited from three MMT clinics in Wuhan, China. These patients completed a standardized questionnaire concerning socio-demographic and clinical data. Pain intensity was assessed with the 5-point Verbal Rating Scale ("Overall, how intense is your pain now?") with responses of: 1 = none, 2 = mild, 3 = moderate, 4 = severe, 5 = very severe. A pain score of three or higher was used to denote clinical significant pain (CSP). The prevalence of CSP in HDPs receiving MMT was 53.6%. Factors significantly associated CSP in multiple logistics regression analysis were old age, marital status of "non-married", unemployment, having religious beliefs, a history of injecting heroin, a high dose of methadone, and more depressive symptoms. Over a half of Chinese HDPs receiving MMT have CSP. Services for HDPs in MMT settings should include periodic screening for pain, psychosocial supports, and professional treatment for pain.

Topics: Adult; Cross-Sectional Studies; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Pain; Prevalence; Public Health Surveillance; Socioeconomic Factors; Young Adult

We examined initiation patterns among different birth cohorts of people who used prescription opioids and heroin because of historical differences in drug use availability. We examined data from a community-based study of persons who inject drugs (n = 483) in California and a general population survey from the National Survey on Drug Use and Health (n = 1264) and found that individuals born after 1980 were more likely than were individuals born before 1980 to initiate opioids through nonmedical use of prescription opioids than heroin.

Topics: Adolescent; Adult; Age of Onset; Aged; Analgesics, Opioid; California; Cohort Studies; Heroin; Humans; Middle Aged; Pain; Prescription Drug Misuse; Substance-Related Disorders; Young Adult

A painful petechial rash developed in a patient after the subcutaneous or intravenous injection of reported black tar heroin. Additional history and the appearance of the skin lesion suggested otherwise.

Topics: Adult; Exanthema; Female; Heroin; Heroin Dependence; Humans; Narcotics; Pain; Skin; Substance Abuse, Intravenous

Pain management in opioid abusers engenders ethical and practical difficulties for clinicians, often resulting in pain mismanagement. Although chronic opioid administration may alter pain states, the presence of pain itself may alter the propensity to self-administer opioids, and previous history of drug abuse comorbid with chronic pain promotes higher rates of opioid misuse. Here, we tested the hypothesis that inflammatory pain leads to increased heroin self-administration resulting from altered mu opioid receptor (MOR) regulation of mesolimbic dopamine (DA) transmission. To this end, the complete Freund's adjuvant (CFA) model of inflammation was used to assess the neurochemical and functional changes induced by inflammatory pain on MOR-mediated mesolimbic DA transmission and on rat intravenous heroin self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. In the presence of inflammatory pain, heroin intake under an FR schedule was increased for high, but attenuated for low, heroin doses with concomitant alterations in mesolimbic MOR function suggested by DA microdialysis. Consistent with the reduction in low dose FR heroin self-administration, inflammatory pain reduced motivation for a low dose of heroin, as measured by responding under a PR schedule of reinforcement, an effect dissociable from high heroin dose PR responding. Together, these results identify a connection between inflammatory pain and loss of MOR function in the mesolimbic dopaminergic pathway that increases intake of high doses of heroin. These findings suggest that pain-induced loss of MOR function in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associated phenotypes.. This study provides critical new insights that show that inflammatory pain alters heroin intake through a desensitization of MORs located within the VTA. These findings expand our knowledge of the interactions between inflammatory pain and opioid abuse liability, and should help to facilitate the development of novel and safer opioid-based strategies for treating chronic pain.

Topics: Action Potentials; Analgesics, Opioid; Animals; Conditioning, Operant; Disease Models, Animal; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Excitatory Amino Acid Antagonists; Glycine Agents; Heroin; Hyperalgesia; Inflammation; Inhibitory Postsynaptic Potentials; Male; Neurons; Pain; Pain Threshold; Quinoxalines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu; Strychnine; Sucrose; Ventral Tegmental Area

Urgent analgesia is essential for all children who present in severe pain, but difficulties in obtaining venous access can delay the use of adequate opiate analgesia. Intranasal diamorphine (IND) is now in use in around 60% of emergency departments and is the preferred choice of analgesia as reported by both parents and healthcare professionals. While IND has similar efficacy to intramuscular morphine in children, no study has compared its use against the current gold standard, intravenous morphine (IVM).. IND was introduced to the Royal Aberdeen Children's Hospital on 24 December 2009. A retrospective case series was constructed to compare its clinical performance with its predecessor IVM. Three unexplored factors were investigated: time to opiate analgesia, the requirement for further analgesia when still in the emergency department and the effect of simple coanalgesia (eg, paracetamol/ibuprofen) on these requirements.. 297 patients were eligible for the study (147 IND, 150 IVM) over a 28-month period. There was a non-significant trend to a longer median time to administration of analgesia in patients receiving IND (p=0.170). Patients who received IND were less likely to require further analgesia (p<0.001). Both groups were less likely to require further analgesia when simple coanalgesia was given (p=0.049).. The authors found no significant difference in time to administration of analgesia between agents, but a learning curve has been identified. Sustained effort should be placed on the use of simple coanalgesia. The clinical performance of IND compares favourably with IVM in children with severe pain, and it remains an appropriate preferred agent.

Topics: Administration, Intranasal; Adolescent; Analgesia; Analgesics, Opioid; Child; Child, Preschool; Drug Therapy, Combination; Emergency Service, Hospital; Female; Heroin; Humans; Infant; Injections, Intravenous; Male; Morphine; Pain; Retrospective Studies; Scotland; Time Factors

Effective urine drug testing requires an understanding of the stability of medications, metabolites and other substances excreted in the urine matrix. When the testing results do not fit the clinical picture, physicians frequently request repeat testing of the original specimen in order to corroborate the results. We determined the stability in urine of various medications, metabolites, and illicit substances commonly requested for testing by physicians treating patients with pain and pain-related disorders.. Quantitative analyses of urine specimens were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two replicates at a high and low concentration were analyzed at time 0, and after 2, 3 and 6 months following storage at +4 °C and -20 °C. At each time interval, the percent difference from time 0 for each analyte was calculated and averaged for each storage condition.. For the majority of medications, the percent differences were within 20% of the original measurement for all 3 storage conditions. All were within 30% of the original measurement after 2, 3 and 6 months in all storage conditions, except for 7-amino-clonazepam, and carboxy-tetrahydrocannabinol.. The findings from the current study confirm that the majority of medications, metabolites, and illicit substances commonly requested for testing by physicians treating patients with pain and pain-related disorders are stable within 20% of the original concentration when stored refrigerated or frozen for up to 6 months. Thus, delayed testing, repeat testing, and add-on testing of urine specimens can yield reliable results for up to 6 months following the urine collection date.

Topics: Amphetamine; Analgesics; Chromatography, Liquid; Drug Stability; Heroin; Humans; Illicit Drugs; Morphine; Pain; Reference Standards; Reproducibility of Results; Substance Abuse Detection; Tandem Mass Spectrometry

Topics: Analgesics, Opioid; Buprenorphine; Cocaine; Drug Overdose; Drug Prescriptions; Health Knowledge, Attitudes, Practice; Heroin; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Substance-Related Disorders; United States

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target, as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma, we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach through the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten.

Topics: Animals; Antibody Specificity; Cattle; Drug Carriers; Enzyme-Linked Immunosorbent Assay; Haptens; Hemocyanins; Heroin; Heroin Dependence; Hot Temperature; Immunoconjugates; Male; Molecular Structure; Morphine; Narcotics; Pain; Psychotropic Drugs; Rats; Rats, Wistar; Secondary Prevention; Self Administration; Serum Albumin, Bovine; Structure-Activity Relationship; Touch; Vaccines

Intranasal opiate analgesia is the first choice in children presenting to paediatric emergency departments with severe pain. A prospective observational study was performed which showed that intranasal fentanyl is a safe effective alternative to diamorphine.

Topics: Administration, Intranasal; Adolescent; Analgesia; Analgesics, Opioid; Child; Child, Preschool; Emergency Service, Hospital; Female; Fentanyl; Heroin; Humans; Infant; Male; Pain; Prospective Studies; Treatment Outcome

Strong opioids such as morphine are rarely accessible in low- and middle-income countries, even for patients with the most severe pain. The three cases reported here from three diverse countries provide examples of the terrible and unnecessary suffering that occurs everyday when this essential, inexpensive, and safe medication is not adequately accessible by patients in pain. The reasons for this lack of accessibility are explored, and ways to resolve the problem are proposed.

Topics: Acquired Immunodeficiency Syndrome; Adult; Analgesics, Opioid; Developing Countries; Dyspnea; Fatal Outcome; Female; Health Services Accessibility; Heroin; Humans; Male; Middle Aged; Morphine; Neoplasm Metastasis; Ovarian Neoplasms; Pain; Palliative Care; Patient Rights; Prostatic Neoplasms; Suicide; Terminally Ill

Topics: Administration, Intranasal; Adult; Analgesics, Opioid; Emergency Medicine; Evidence-Based Medicine; Female; Fentanyl; Fractures, Bone; Heroin; Humans; Infusions, Intravenous; Joint Dislocations; Morphine; Pain

Topics: Analgesics, Opioid; Australia; Contracts; Drug Prescriptions; Heroin; Humans; Legislation, Drug; Opioid-Related Disorders; Pain; Prescription Drugs

Identify opioids prescribed, preferred routes, and doses among children with incurable cancer.. Prospective survey with monthly questionnaires regarding patients 0 to 19 years old from oncology centers. Data were collected by professionals on each patient for 6 months or until death, and analyzed from patients who died. Impact of tumor was analyzed with Kruskal-Wallis and Mann-Whitney tests. Major opioid dosages are expressed as oral morphine equivalents.. Of 185 children recruited, 164 (88 boys, 76 girls) died. Mean palliative care duration was 67 days. One hundred forty-seven (89.6%) received major opioids. Morphine, diamorphine, and fentanyl were prescribed in 75%, 57.9%, and 11.6%, respectively. Seventy-three (44.5%) received >1 major opioid. Median monthly maximum doses prescribed rose from 2.1 mg/kg/24 h (study entry) to 4.4 mg/kg/24 h (death) (P < .001); overall variable (0.09-1500 mg/kg/24 h, median 3.7 mg/kg/24 h). Opioids were given by the oral (117/164, 71.3%), intravenous (68/164, 41.5%), subcutaneous (40, 28%), rectal (20, 12.2%), and transdermal (18, 11%) routes. There was a shift to intravenous use as death approached. Numbers within each tumor group were too small to show significance. Children with solid tumors outside the central nervous system were likely to receive more opioids, be given multiple different opioids, and receive opioids in the last month.. The study shows the United Kingdom practice of opioid use and provides comparator data for practice in children's palliative medicine.

Topics: Administration, Oral; Administration, Rectal; Adolescent; Adult; Analgesics, Opioid; Child; Child, Preschool; Drug Prescriptions; Female; Fentanyl; Heroin; Humans; Infant; Infusions, Intravenous; Injections, Subcutaneous; Male; Morphine; Neoplasms; Pain; Palliative Care; Prospective Studies; Research Design; Surveys and Questionnaires; Therapeutic Equivalency; United Kingdom

Neuropathic pain is associated with several sensory abnormalities, including allodynia as well as spontaneous pain. Opioid intake in neuropathic pain patients is motivated by alleviation of both pain and allodynia. However, laboratory animal studies rely almost exclusively on reflexive withdrawal measures of allodynia. The authors examined the pharmacology of self-regulated intake of opioids in rats with or without nerve injury and compared the rate of drug intake to reversal of allodynia.. Rats were implanted with intravenous catheters, and the L5 and L6 spinal nerves were ligated in half of these animals. Rats were then trained to self-administer a commonly abused opioid (heroin) and commonly prescribed opioids (morphine, fentanyl, hydromorphone, and methadone). In addition, rats trained to self-administer heroin were given either clonidine or adenosine spinally before self-administration sessions to assess opioid-sparing effects.. Nerve injury significantly decreased the reinforcing effects of low doses of opioids, and only doses of each opioid that reduced mechanical hypersensitivity maintained self-administration after spinal nerve ligation. The rate of drug consumption was correlated with the duration of the antiallodynic effect for each dose of opioid. Intrathecal administration of clonidine or adenosine reversed mechanical hypersensitivity, but only clonidine reduced heroin self-administration in rats with spinal nerve ligation.. Opioid self-administration is significantly altered by nerve injury, with rate of drug intake being correlated with reversal of allodynia. Intrathecal clonidine, but not adenosine, produces opioid-sparing effects in self-administering rats. The neurobiologic mechanisms that regulate opioid consumption in rats therefore seem to be altered after nerve injury.

Topics: Adenosine; Analgesics, Opioid; Animals; Clonidine; Dose-Response Relationship, Drug; Fentanyl; Heroin; Hydromorphone; Infusions, Intravenous; Injections, Spinal; Male; Methadone; Morphine; Neuralgia; Pain; Rats; Rats, Inbred F344; Self Administration

The purpose of this study was the evaluation of clinical heroin symptoms and buprenorphine drug addiction in the withdrawal period with the purpose of their comparison, study of parameters of bone metabolism in the both groups. In the study group were included 40 patients with heroin and 27 with buprenorphine addiction in the period of abstinence. Our investigations have shown, that in the both groups, among clinical symptoms ossalgias, arthralgias and mialgias attributes to the expressed dysfunction of vegetative system, were most prominent. Decrease of sexual functions was found in half of inspected patients. Biochemical investigations have shown intensive clearance of calcium with the urine that indicates intensifying resorbtion processes in the bone tissue. Symptoms of hypogonadism were accompanied by the decrease of the level of testosterone in the blood. Parameters of mineral consistency of the bone tissue was decreased both in patients with heroin and buprenorphine addiction.

Topics: Behavioral Symptoms; Biomarkers; Bone and Bones; Bone Density; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Morphine Dependence; Pain; Radiography; Substance Withdrawal Syndrome

To determine the proportion of emergency departments in the UK that use modern pharmacological methods of pain and anxiety control in children, such as analgesia with intranasal diamorphine, procedural sedation using ketamine or midazolam, and adrenaline-cocaine gel, TAC or LAT for anaesthetising wounds in children.. A survey UK Emergency Departments conducted by email, post and telephone.. Of the 183 (70%) of UK Emergency Departments responding, sedation is achieved using ketamine in 27% and using midazolam in 54%. In 55% of emergency departments intranasal diamorphine is used for analgesia and 41% use at least one of the topical local-anaesthetic mixtures to anaesthetise wounds before suturing.. About half of UK emergency departments use modern pharmacological methods of procedural pain control in children. There is still considerable potential to improve the management of pain in children.

Topics: Administration, Intranasal; Administration, Topical; Analgesics; Anesthesia, Local; Child; Emergency Medicine; Emergency Service, Hospital; Health Care Surveys; Heroin; Humans; Ketamine; Midazolam; Pain; Pain Management; Practice Patterns, Physicians'; United Kingdom

(1) Methadone is an opiate used for replacement therapy of opiate addiction that causes dose-dependent QT prolongation. (2) Severe ventricular arrhythmias such as torsades de pointes have been reported, usually in patients on high doses (100 mg to 400 mg/day). (3) Methadone has a long plasma elimination half-life, and this poses a risk of accumulation. Accumulation is especially problematic when the dose is increased too rapidly. Combining methadone with a CYP 3A4 inhibitor increases the risk of torsades de pointes, as methadone is metabolised by this enzyme system. (4) Factors potentially predisposing patients to torsades de pointes must be analysed in each case; these include preexisting bradycardia, congenital QT prolongation, hypokalemia, and concomitant use of other drugs inducing QT prolongation. (5) This adverse effect has also been reported with levacetylmethadol (another opiate) and with heroin. It does not seem to occur with buprenorphine.

Topics: Analgesics, Opioid; Aryl Hydrocarbon Hydroxylases; Drug Interactions; Heroin; Humans; Hypokalemia; Long QT Syndrome; Methadone; Narcotics; Opioid-Related Disorders; Pain; Retrospective Studies; Risk Factors; Switzerland; Torsades de Pointes

The present study examined the pharmacology of dihydromorphine, 6-acetyldihydromorphine and dihydroheroin (3,6-diacetyldihydromorphine). Like morphine, dihydromorphine and its acetylated derivatives all were highly selective mu-opioids in receptor binding assays. All the compounds were potent mu-selective analgesics, as shown by their sensitivity towards the mu-selective opioid receptor antagonists naloxonazine and beta-funaltrexamine. However, the actions of dihydromorphine and its analogs were readily distinguished from those of morphine, differences that were surprising in view of the very limited structural differences among them that consisted of only the reduction of the 7,8-double bond. Like heroin and morphine-6beta-glucuronide, the analgesic actions of dihydromorphine and its two acetylated derivatives were antagonized by 3-O-methylnaltrexone at a dose that was inactive against morphine analgesia. Antisense mapping also distinguished between morphine and the dihydromorphine compounds. Antisense oligodeoxynucleotides targeting exon 2 of the cloned MOR-1 gene decreased dihydromorphine analgesia and that of its acetylated derivatives, but not morphine analgesia. Conversely, the exon 1 antisense that effectively lowered morphine analgesia was inactive against dihydromorphine and its analogs. Finally, dihydromorphine and its analogs retained their analgesic activity in a mouse model of morphine tolerance, consistent with incomplete cross-tolerance. Together, these findings imply that the mu-opioid receptor mechanisms mediating the analgesic actions of dihydromorphine and its acetylated analogs are distinct from morphine and more similar to those of heroin and morphine-6beta-glucuronide.

Topics: Analgesics, Opioid; Animals; Dihydromorphine; Drug Tolerance; Heating; Heroin; Injections, Subcutaneous; Male; Mice; Mice, Inbred ICR; Morphine; Oligonucleotides, Antisense; Pain; Receptors, Opioid, mu; Reverse Transcriptase Polymerase Chain Reaction; Structure-Activity Relationship

Concern exists over recent unexplained deaths among intravenous drug users. This report describes a patient with crepitant cellulitis who was admitted complaining of severe pain in the right forearm. Ultrasonography demonstrated gas in the tissues and he was referred for early surgical debridement of the arm. He was treated with intravenous benzyl penicillin, gentamicin and metronidazole and made a full recovery. Aspirate samples grew Bacillus cereus, morphologically similar to the isolate obtained from a sample of the patient's own heroin. Antibiogram and API 50CHB profiles were also similar. Further typing included 'H' flagellar serotyping, which found both blood and heroin strains to be non-typable, and amplified fragment polymorphism analysis, which showed that the strains were indistinguishable. Genotyping of two selected genes from B. cereus confirmed almost certain identity between the two strains. This case illustrates the potential virulence of B. cereus when inoculated into tissues, and to our knowledge, is the first report to demonstrate a conclusive microbiological link between contaminated heroin and serious sepsis in a drug user due to B. cereus.

Topics: Adult; Anti-Bacterial Agents; Bacillus cereus; Cellulitis; Forearm; Genotype; Gentamicins; Heroin; Humans; Injections, Intravenous; Male; Metronidazole; Pain; Penicillins; Substance Abuse, Intravenous; Ultrasonography

Topics: Administration, Intranasal; Analgesics, Opioid; Child, Preschool; Clavicle; Fractures, Bone; Heroin; Humans; Male; Pain; Secondary Prevention

Mechanisms underlying the development of acute tolerance to the analgesic effect of opiates were investigated. In the rat tail-flick test, administration of naloxone (1 mg/kg, s.c.) 40 min after heroin (1 mg/kg, s.c.) was shown to induce hyperalgesia, indicative of a short-onset, opiate-activated pain facilitatory systems masking the opiate analgesia. Pretreatment with the N-methyl-D-aspartate receptor antagonist dizocilpine maleate blocked, in a dose-dependent manner, the naloxone-induced hyperalgesia and potentiated the heroin-induced analgesia. Using a schedule of two successive injections of 1 mg/kg heroin, acute tolerance was indicated by a marked reduction (-52%) in analgesia induced by the second dose. After pretreatment with dizocilpine maleate, the acute tolerance was abolished and the analgesic effects of both injections of heroin were strongly potentiated. These observations indicate that acute tolerance appears after the first exposure to opiates and stems from opiate activation of N-methyl-D-aspartate-dependent pain facilitatory systems.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Dizocilpine Maleate; Drug Tolerance; Heroin; Hyperalgesia; Male; Naloxone; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Reaction Time

Acute dependence, defined as a precipitation of somatic signs by an antagonist, may occur after a single administration of an opiate drug. Because hyperalgesia is a consistent sign of the withdrawal syndrome, we tested the effectiveness of heroin, an opiate used by addicts, to induce pain facilitation even after a first exposure to the drug. In opiate-naive rats, subcutaneous injection of heroin induced analgesia followed by allodynia, a decrease in pain threshold. This latter phenomenon was observed in the absence of noxious stimuli and lasted several days. An N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 prevented such long-lasting allodynia. These results suggest that allodynia is an early sign reflecting neural plasticity associated with the development of dependence.

Topics: Animals; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Heroin; Male; Narcotics; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Vocalization, Animal

Neuropathic pain has been suggested to be resistant to treatment with opiates. Such perceived lack of opioid responsiveness may be due to the dose-range over which specific opioid compounds have been studied as well as the efficacy of these compounds. Dihydroetorphine is a novel opiate that demonstrates significantly greater analgesic potency compared to morphine, and which also demonstrates diminished capacity for producing physical dependence in laboratory animals. The present study compared the intravenous (i.v.) efficacy, potency and duration of action of dihydroetorphine, fentanyl, heroin and morphine in producing anti-allodynic actions in a rat model of neuropathic pain (ligation of the L5/L6 nerve roots). All compounds produced significant anti-allodynic activity with dihydroetorphine being the most potent (A50 of 0.2 microg kg(-1), i.v.). Morphine was approximately 7440 times less potent than dihydroetorphine while heroin and fentanyl were approximately 163.5 and 6.9 times less potent in producing anti-allodynic actions. Dihydroetorphine also showed a maximal effect at 0.6 microg kg(-1) in all animals tested, while 100 microg kg(-1) was required for heroin to produce a maximal effect. Fentanyl and morphine did not elicit a maximum anti-allodynic response (74 and 76% maximum possible effect (%MPE), respectively). As expected, fentanyl showed a relatively brief duration of action (approximately 20 min at the highest tested dose), while dihydroetorphine and morphine demonstrated anti-allodynic actions for up to 45 min. Heroin had the longest duration of action, producing significant anti-allodynic effects for up to 90 min. These data show that dihydroetorphine and heroin produce potent and long-lasting anti-allodynic actions in this model. Additionally, in contrast to morphine and fentanyl, both dihydroetorphine and heroin were able to achieve a maximal response. The remarkable potency, maximal efficacy and duration of action of these compounds, particularly dihydroetorphine, suggests that these compounds may warrant further examination as potential therapeutic treatments for neuropathic pain states.

Topics: Analgesics, Opioid; Animals; Drug Evaluation; Etorphine; Fentanyl; Heroin; Infusions, Intravenous; Ligation; Male; Morphine; Nerve Compression Syndromes; Pain; Rats; Rats, Inbred F344; Spinal Nerves

CD-1 mice were treated intravenously with streptozotocin, 200 mg/kg, and tested 2 weeks later or treated with 60 mg/kg and tested 3 days later. Both treatments changed the tail flick response of heroin and 6-monoacetylmorphine (6 MAM) given intracerebroventricularly from a mu- to delta-opioid receptor-mediated action as determined by differential effects of opioid receptor antagonists. The response to morphine remained mu. Heroin and 6 MAM responses involved delta1 (inhibited by 7-benzylidenenaltrexone) and delta2 (inhibited by naltriben) receptors, respectively. These delta-agonist actions did not synergize with the mu-agonist action of morphine in the diabetic mice. The expected synergism between the delta agonist, [D-Pen2-D-Pen5]enkephalin (DPDPE), and morphine was not obtained in diabetic mice. Thus, diabetes disrupted the purported mu/delta-coupled response. In nondiabetic CD-1 mice, heroin and 6 MAM produced a different mu-receptor response (not inhibited by naloxonazine) from that of morphine (inhibited by naloxonazine). Also, these mu actions, unlike that of morphine, did not synergize with DPDPE. The unique receptor actions and changes produced by streptozotocin suggest that extrinsic in addition to genetic factors influence the opioid receptor selectivity of heroin and 6 MAM.

Topics: Analgesics, Opioid; Animals; Anti-Bacterial Agents; Benzylidene Compounds; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Drug Interactions; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Heroin; Injections, Intraventricular; Male; Mice; Morphine; Morphine Derivatives; Naloxone; Naltrexone; Narcotic Antagonists; Nociceptors; Pain; Receptors, Opioid, delta; Receptors, Opioid, mu; Streptozocin; Time Factors

We report a previously undescribed complication of long-term epidural catheter placement for the administration of analgesia in terminal malignancy. Spinal cord compression resulted from a drug-related precipitate forming around the epidural catheter tip, which was successfully treated by surgical decompression.

Topics: Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Catheters, Indwelling; Decompression, Surgical; Heroin; Humans; Lymphoma, B-Cell; Male; Middle Aged; Pain; Pancreatic Neoplasms; Spinal Cord Compression

Topics: Adult; Analgesics; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Arm; Combined Modality Therapy; Drug Overdose; Edema; Heroin; Heroin Dependence; Humans; Male; Methylprednisolone; Muscular Diseases; Oxygen Inhalation Therapy; Pain; Rhabdomyolysis; Syndrome

What are we talking about when we speak of pain in a drug abuser? Physical and psychiatric pain are confounded. Heroin anesthesizes pain in general and grief pain in particular. Is there a relationship between stomatology and pain? A drug abuser's psychopathology evolves over time. The biological effects of morphine, compared with the biological effects of subutex and methadone, are sufficient in themselves to justify their use in substitution therapy. But in practice, the psychopathological situation of the drug abuser requires us to construct a close rigorous relationship to maintain treatment. Once this relationship has been constructed within the frame work of the substitution therapy, the drug abuser will accept dental, medical and surgical care.

Topics: Anesthesia; Comprehensive Health Care; Heroin; Heroin Dependence; Humans; Methadone; Morphine; Narcotics; Pain; Physician-Patient Relations; Substance Abuse Treatment Centers; Substance-Related Disorders

Neuropeptide FF (NPFF) is a mammalian FMRFamide-like octapeptide with antiopioid properties that inhibits morphine-induced analgesia but also produces hyperalgesia. In the present study, a series of three experiments was carried out to investigate the interactions between opioid receptor stimulation and antiopioid systems. First, by using in vitro superfusion system with rat spinal cord slices, we showed that morphine stimulated NPFF release in a dose-dependent manner. The stimulating effect which was observed with morphine concentrations as low as 100 fM reached a maximum at 0.1 nM, then decreased and was ineffective at 10 microM. The morphine-induced release of NPFF was abolished by naloxone (1 microM) but unaltered by tetrodotoxin. Second, by an in vivo approach, we showed that a single heroin administration (2.5 mg/kg, s.c.) elicited in 30 min a drastic drop (38%) in spinal NPFF content. In a third experiment, we evaluated the capacity of naloxone in revealing an antiopioid component associated with opioid receptor stimulation. The administration of naloxone (1 mg/kg, s.c..) 25 min following that of heroin (2.5 mg/kg, s.c.) not only abolished the heroin-induced increase of tail-flick latency, but also lowered it under the basal value by 30%. These results indicate that opioid receptor stimulation activates both pain inhibitory and pain facilitatory systems in which NPFF may play a significant role and that opiate-induced analgesia is always partly masked.

Topics: Animals; Heroin; In Vitro Techniques; Male; Morphine; Naloxone; Narcotic Antagonists; Neuropeptides; Oligopeptides; Pain; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Opioid; Spinal Cord; Tetrodotoxin

We report an ulcerative skin reaction resulting from a subcutaneous infusion of isotonic methotrimeprazine and diamorphine. Skin reactions are a recognized side effect of this treatment, although they are reduced by the use of the isotonic formulation of methotrimeprazine. Frank ulceration has not been previously reported. It occurred in our patient despite low doses of diamorphine and methotrimeprazine, an isotonic formulation, and a short infusion time.

Topics: Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Female; Heroin; Humans; Injections, Subcutaneous; Isotonic Solutions; Methotrimeprazine; Pain; Palliative Care; Skin Ulcer

The purpose of this study was to determine which delta (delta) opioid receptor subtype, delta 1 or delta 2, was involved in producing the antinociceptive action of heroin and 6-monacetylmorphine (MAM) in Swiss Webster mice. Previous work from this laboratory established that heroin and MAM, given intracerebroventricularly (i.c.v.) in Swiss Webster mice, produce antinociception through activation of supraspinal delta receptors. Naltrindole, but not naloxone or nor-binaltorphimine, antagonizes the inhibitory action of heroin and MAM in the tail-flick test. Recent literature documents the occurrence of subtypes of the delta opioid receptor and the availability of selective antagonists. 7-Benzylidenenaltrexone (BNTX) antagonizes the antinociception induced by delta 1 receptor agonists without affecting that induced by delta 2 receptor agonists. Naltriben (NTB) selectively inhibits delta 2- but not delta 1-induced antinociception. In the present study BNTX and NTB were administered i.c.v. with heroin and MAM to determine the delta receptor subtype responsible for inhibition of the tail-flick response in Swiss Webster mice. The ED50 for heroin-induced antinociception was increased 19-fold by BNTX and was not altered by NTB administration. On the other hand, the ED50 value of MAM was increased 3-fold by NTB and was not altered by BNTX administration. These results suggest that heroin activated supraspinal delta 1 receptors and MAM acted on supraspinal delta 2 receptors to produce antinociception in Swiss Webster mice.

Topics: Animals; Benzylidene Compounds; Heroin; Male; Mice; Morphine Derivatives; Naltrexone; Pain; Receptors, Opioid, delta

Topics: Heroin; Humans; Legislation, Drug; Neoplasms; Pain; Program Development; Wisconsin

Topics: Beneficence; Drug and Narcotic Control; Ethics, Pharmacy; Heroin; Humans; Internationality; Moral Obligations; Pain; Public Opinion; Risk Assessment; Social Perception

Topics: Drug and Narcotic Control; Heroin; Humans; Internationality; Pain; Pain, Intractable; Pharmacists; Risk Assessment; Social Responsibility; United States

Topics: Antiemetics; Drug Combinations; Heroin; Humans; Infusion Pumps; Injections, Subcutaneous; Pain

Topics: Heroin; Humans; Neoplasms; Pain; Palliative Care

Topics: Australia; Drug and Narcotic Control; Heroin; Humans; Pain

Topics: Blood Pressure; Cyclizine; Heroin; Humans; Hypotension, Orthostatic; Injections, Intravenous; Morphine; Myocardial Infarction; Pain

Topics: Adult; Anxiety; Cocaine; Heroin; Humans; Male; Middle Aged; Pain; Pain Measurement; Substance-Related Disorders

Topics: Administration, Oral; Age Factors; Analgesics, Opioid; Blood Circulation; Drug Interactions; Half-Life; Heroin; Humans; Infusions, Parenteral; Injections; Injections, Intramuscular; Injections, Spinal; Intestines; Kinetics; Liver; Metabolic Clearance Rate; Morphine; Pain; Pain, Intractable; Respiration

Topics: Heroin; Humans; Infusions, Parenteral; Neoplasms; Pain

Topics: Heroin; Humans; Neoplasms; Pain

Topics: Heroin; Humans; Meperidine; Neoplasms; Pain

Topics: Canada; Health Occupations; Heroin; Humans; Legislation, Drug; Neoplasms; Pain; Palliative Care

Topics: Analgesics; Analgesics, Opioid; Heroin; Humans; Morphine; Neoplasms; Pain

Maintenance of intravenous heroin self-administration and the degree of tolerance to the analgesic effect of self-injected heroin were simultaneously measured in heroin-tolerant rats. Subcutaneous injection of oxytocin (OXT-(1-9)) and of its behaviorally active fragments desglycinamide9-oxytocin (OXT-(1-8)) and [pGlu4,Cyt6]-oxytocin-(4-8) (OXT-(4-8)) decreased the amount of heroin self-injected. The C-terminal tripeptide of oxytocin (prolyl-leucyl-glycinamide, PLG, OXT-(7-9)) and desglycinamide9-[Arg]8-vasopressin (AVP-(1-8] were ineffective in this respect. In spite of the lower amount of self-injected heroin after pretreatment with oxytocin fragments, no differences in the antinociceptive effect of self-injected heroin, as assessed by the lick response using a hot plate device, were observed after pretreatment with placebo and oxytocin fragments. These findings suggest that oxytocin and some of its behaviorally active fragments attenuate heroin tolerance and that this effect may result in a diminished heroin intake in tolerant animals self-injecting heroin.

Topics: Analgesics; Animals; Drug Tolerance; Heroin; Male; Oxytocin; Pain; Peptide Fragments; Rats; Rats, Inbred Strains; Self Administration

Topics: Heroin; Humans; Neoplasms; Pain; Palliative Care; Risk Assessment; Terminal Care; United Kingdom; United States

We measured blood concentrations of heroin and its active metabolites, 6-acetylmorphine and morphine, serially in 11 patients with chronic pain (9 of whom had cancer) after intravenous injection, intravenous infusion, intramuscular injection, and an oral dose of heroin hydrochloride. Parenteral heroin provided measureable blood levels of heroin, 6-acetylmorphine, and morphine. Blood levels of heroin and 6-acetylmorphine reached their maximal concentrations within minutes and were cleared rapidly. The mean half-life of heroin (+/- S.D.) after intravenous injection or infusion was only 3.0 +/- 1.3 minutes, and the mean clearance of heroin from the blood at apparent steady state was 30.8 +/- 2.1 ml per kilogram of body weight per minute. Morphine levels rose more gradually, and morphine was cleared much more slowly. Oral administration of heroin resulted in measurable blood levels of morphine but not of heroin or 6-acetylmorphine. The amount of circulating morphine provided by an oral dose of heroin was only 79 per cent of that available from an equal amount of morphine. We conclude that heroin is a pro-drug that serves to determine the distribution of its active metabolites. Parenteral heroin is rapidly converted to 6-acetylmorphine, which contributes to rapid pain relief. Oral heroin is converted to morphine and appears to be an inefficient means of providing morphine to the systemic circulation.

Topics: Administration, Oral; Adult; Aged; Biological Availability; Chronic Disease; Female; Half-Life; Heroin; Humans; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Kinetics; Male; Middle Aged; Morphine; Morphine Derivatives; Pain; Pain, Intractable; Time Factors

Topics: Heroin; Humans; Legislation, Drug; Pain; Palliative Care; Terminal Care; United States

Endogenous hyperprolactinaemia induced by anterior pituitary transplantation under the kidney capsule has been found to reduce the behavioural responsiveness to electrical footshock and to increase morphine-induced analgesia. The apparent analgesic effect of prolactin has been related to the stimulation of nigro-striatal dopaminergic transmission, as suggested by the increase in striatal dopamine turnover observed in hyperprolactinaemic rats. It seems likely that central opiate system is involved in the behavioural effects of prolactin. Thus, naloxone prevents the effects of hyperprolactinaemia on footshock responsiveness and heroin self-administration is decreased in hyperprolactinaemic rats.

Topics: Animals; Electroshock; Heroin; Male; Morphine; Pain; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Inbred Strains; Receptors, Opioid; Sensory Thresholds

Topics: Attitude; Canada; Government Regulation; Heroin; Humans; Neoplasms; Pain; Physicians; Social Control, Formal; Terminal Care; Terminally Ill

Topics: Analgesics, Opioid; Attitude; Euthanasia, Passive; Heroin; Humans; Life Support Care; Moral Obligations; Neoplasms; Pain; Pharmaceutical Preparations; Physicians; Risk; Risk Assessment; Social Responsibility; Stress, Psychological; Terminal Care; Treatment Refusal

Topics: Heroin; Humans; Injections, Spinal; Pain

Topics: Heroin; Humans; Morphine; Neoplasms; Pain; Palliative Care

The scarce or absent analgesic effect exhibited by morphine on pain from migraine attack and the poor inhibition of the spasmogenic effect of 5-HT (tested on the hand dorsal vein, computerized venotest) suggest the hypothesis of an opioid receptor deficiency in headache sufferers. Since endogenous opioids control the nociception, the sense of well being, and the vegetative balance, an opioid receptoral hypofunction could be the background of the headache and central panalgia, where the trinity pain, anhedonia, and dysautonomia are the characteristic features.

Topics: Animals; Haplorhini; Headache; Heroin; Humans; Migraine Disorders; Pain; Receptors, Opioid; Substance Withdrawal Syndrome

Heroin hydrochloride is approximately twice as potent as morphine sulfate, and acts slightly faster but for a shorter duration than morphine. Although patients with chronic pain due to advanced cancer differ from cancer patients with postoperative pain in terms of their degree of tolerance to the analgesic effects of morphine and heroin and their reports of various elements of mood, there is, thus far, no indication that heroin has any unique advantage over morphine in terms of side effect occurrence or effects on mood at equianalgesic doses. Both drugs improve mood provided they are administered in doses which result in analgesia. While there appears to be some slight difference in the spectrum of side effects observed after heroin as compared to morphine, heroin and morphine share the most common side effects. The incidence of side effects following both drugs appear to be highest among those effects which are primarily somatic and undesirable. The use of visual analog scales concurrent with categorical pain and pain relief scores provides a means for the finer estimation of relative analgesic potency and time action. The results of these studies are in general agreement with those of other investigators. Where apparent differences exist they can usually be explained on the bases of differences in methods and subject populations.

Topics: Adult; Aged; Analgesics; Chronic Disease; Female; Heroin; Humans; Injections, Intramuscular; Levorphanol; Male; Meperidine; Middle Aged; Morphine; Neoplasms; Pain; Postoperative Complications

Topics: Amphetamines; Behavior; Cannabis; Drug Therapy; Epilepsy; Heroin; Humans; Illicit Drugs; Lysergic Acid Diethylamide; Mental Disorders; Nausea; Obesity; Pain; Vomiting

Topics: Heroin; Humans; Pain

Topics: Analgesics, Opioid; Animals; Body Weight; Delayed-Action Preparations; Heroin; Hydrolyzable Tannins; Hydromorphone; Male; Pain; Rats; Solubility; Time Factors; Zinc

Topics: Attitude to Death; Family; Heroin; Hospices; Hospitals; Humans; Organizational Policy; Pain; Social Work; Terminal Care

Topics: Civil Rights; Heroin; Humans; Jurisprudence; Neoplasms; Pain; Pharmaceutical Preparations; Privacy; Risk; Risk Assessment; Supreme Court Decisions; Terminal Care; Terminally Ill; United Kingdom; United States

Topics: Cannabis; Dronabinol; Drug Prescriptions; Heroin; Humans; Legislation, Drug; Pain; Research; United States; United States Food and Drug Administration

Topics: Heroin; Humans; Morphine; Neoplasms; Pain

Topics: Cannabis; Heroin; Humans; Neoplasms; Pain; Pharmaceutical Preparations; Terminal Care

Topics: Government Regulation; Heroin; Humans; Neoplasms; Organizational Policy; Pain; Pharmaceutical Preparations; Physicians; Politics; Social Control, Formal; Societies; Stress, Psychological; Terminal Care; Terminally Ill; United Kingdom; United States

Topics: Government Regulation; Heroin; Humans; Pain; Social Control, Formal; Stress, Psychological; Substance-Related Disorders; Terminal Care; Terminally Ill

Topics: Administration, Oral; Chronic Disease; Heroin; Humans; Injections, Intramuscular; Legislation, Drug; Morphine; Pain; Pain, Intractable; Research Design; United States; United States Food and Drug Administration

Topics: Chronic Disease; Heroin; Heroin Dependence; Humans; Pain; Pain, Intractable

Topics: Heroin; Humans; Legislation, Drug; Pain; United States

Topics: Analgesics, Opioid; Attitude; Heroin; Humans; National Institutes of Health (U.S.); Neoplasms; Pain; Palliative Care; Public Opinion; United States

During a recent 5-month period, 16 intravenous heroin users were hospitalized with a previously unrecognized complication of drug abuse. The characteristic symptoms were similar in all patients and included fever, paraspinal myalgias, and periarthritis. There was no evidence of bacterial infection, hepatitis, or drug abstinence as the cause of these musculoskeletal symptoms. Continued heroin use was associated with progressive musculoskeletal symptoms, while discontinuation of heroin use resulted in complete recovery. Antibiotics did not affect the outcome, and the syndrome was self-limited in all hospitalized patients. The pathogenesis of this syndrome is unknown but may be related to the heroin, which was described as brown by the patients, or an adulterant.

Topics: Adult; Anti-Bacterial Agents; Heroin; Heroin Dependence; Humans; Length of Stay; Male; Muscular Diseases; Pain; Periarthritis; Spasm; Spondylitis

Topics: Analgesics; Diazepam; Heart; Hemodynamics; Heroin; Humans; Hydromorphone; Meperidine; Methadone; Morphine; Myocardial Infarction; Nitrogen Oxides; Pain; Pentazocine; Respiration

Topics: Cyclazocine; Cyclopropanes; Drug Evaluation; Female; Heroin; Heroin Dependence; Humans; Male; Morphine Derivatives; Naloxone; Narcotic Antagonists; Opium; Pain; Pupil; Respiration; Sleep; Substance-Related Disorders

Topics: Analgesics; Heroin; Humans; Morphine; Myocardial Infarction; Pain; Pentazocine

Topics: Community Pharmacy Services; Heroin; Heroin Dependence; Humans; Legislation, Drug; Methadone; Pain; Pharmacy Service, Hospital; Substance-Related Disorders; United States; United States Food and Drug Administration

Topics: Adult; Cardiac Surgical Procedures; Curettage; Dextropropoxyphene; Dilatation; Female; Fracture Fixation; Heroin; Humans; Hysterectomy; Male; Meperidine; Methadone; Orthopedics; Pain; Pentazocine; Substance Withdrawal Syndrome; Substance-Related Disorders; Surgery, Oral; Surgical Procedures, Operative

Topics: Adolescent; Adult; Calcium; Gluconates; Heroin; Humans; Injections, Intravenous; Male; Pain; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: American Medical Association; Female; Health Education; Heroin; Humans; Legislation, Drug; Methadone; Morphinans; Morphine; Morphine Dependence; Pain; Personality; Pregnancy; Pregnancy Complications; Socioeconomic Factors; Substance Withdrawal Syndrome; United States

Topics: Adult; Aged; Anticonvulsants; Depression; Diagnosis, Differential; Ergotamine; Face; Facial Neuralgia; Female; Glossopharyngeal Nerve; Heroin; Herpes Zoster; Humans; Intracranial Aneurysm; Male; Middle Aged; Migraine Disorders; Nasopharyngeal Neoplasms; Pain; Temporomandibular Joint Dysfunction Syndrome; Trigeminal Neuralgia

Topics: Analgesics; Heroin; Humans; Morphine; Narcotic Antagonists; Pain; Phenothiazines; Postoperative Care; Postoperative Complications

Topics: Adrenalectomy; Androgens; Breast Neoplasms; Busulfan; Chlorambucil; Estrogens; Heroin; Hormones; Humans; Hypophysectomy; Male; Morphine; Neoplasm Metastasis; Neoplasms; Pain; Palliative Care; Prostatic Neoplasms; Surgical Procedures, Operative; Thiotepa; Toxicology

Topics: Analgesia; Analgesics; Anesthesia; Anesthesia and Analgesia; Heroin; Humans; Morphine; Pain; Potassium