naloxone and Fatigue-Syndrome--Chronic

Opioid painkiller dependence is a growing problem and best-practice management is not well defined. We report a case of a young woman exhibiting dependence on codeine, originally prescribed for myalgic encephalopathy, after escalating use over a 10-year period. In 2012, a consultation with a new general practitioner, who had extensive experience of patients with substance abuse, revealed the underlying dependence. After building trust for 6 months, she was able to admit to medication abuse, and was referred to the community drug and alcohol team. On presentation to the team, the patient had no pain issues and the dihydrocodeine use--600 tablets/week--solely reflected her dependence. The patient successfully underwent rapid induction with buprenorphine/naloxone as opioid substitution treatment over 2 days. She is currently stable, engaged with recovery support services and psychosocial counselling, and has just returned to work. She is maintained on a therapeutic dose of buprenorphine 10 mg/naloxone 2.5 mg.

Topics: Acetaminophen; Analgesics, Opioid; Buprenorphine; Chronic Pain; Codeine; Counseling; Fatigue Syndrome, Chronic; Female; Follow-Up Studies; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Primary Health Care; Risk Assessment; Severity of Illness Index; Treatment Outcome; Young Adult

Disturbance of the HPA axis may be important in the pathophysiology of chronic fatigue syndrome (CFS) and fibromyalgia. Symptoms may be due to: (1) low circulating cortisol; (2) disturbance of central neurotransmitters; or (3) disturbance of the relationship between cortisol and central neurotransmitter function. Accumulating evidence of the complex relationship between cortisol and 5-HT function, make some form of hypothesis (3) most likely. We review the methodology and results of studies of the HPA and other neuroendocrine axes in CFS.. Medline, Embase and Psychlit were searched using the Cochrane Collaboration strategy. A search was also performed on the King's College CFS database, which includes over 3000 relevant references, and a citation analysis was run on the key paper (Demitrack et al. 1991).. One-third of the studies reporting baseline cortisol found it to be significantly low, usually in one-third of patients. Methodological differences may account for some of the varying results. More consistent is the finding of reduced HPA function, and enhanced 5-HT function on neuroendocrine challenge tests. The opioid system, and arginine vasopressin (AVP) may also be abnormal, though the growth hormone (GH) axis appears to be intact, in CFS.. The significance of these changes, remains unclear. We have little understanding of how neuroendocrine changes relate to the experience of symptoms, and it is unclear whether these changes are primary, or secondary to behavioural changes in sleep or exercise. Longitudinal studies of populations at risk for CFS will help to resolve these issues.

Topics: Adrenocorticotropic Hormone; Circadian Rhythm; Fatigue Syndrome, Chronic; Fibromyalgia; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Naloxone; Narcotic Antagonists; Pituitary-Adrenal System; Serotonin; Vasopressins

Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown.. A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten chronic fatigue syndrome (CFS)/fibromyalgia (FM) patients, 11 rheumatoid arthritis (RA) patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/mL Naloxone) and placebo (2 mL Aqua) group. Pressure pain thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned pain modulation (CPM) efficacy and deep tissue pain pressure were assessed by adding ischemic occlusion at the opposite upper arm.. Deep tissue pain pressure was lower and temporal summation higher in CFS/FM (P = 0.002 respectively P = 0.010) and RA patients (P = 0.011 respectively P = 0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (P time = 0.034). Accordingly, PPTs increased after placebo (P time = 0.015), and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, deep tissue pain, temporal summation or CPM in the control group.. This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced deep tissue pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA.

Topics: Adult; Analgesics, Opioid; Arthritis, Rheumatoid; Central Nervous System Sensitization; Cross-Over Studies; Double-Blind Method; Fatigue Syndrome, Chronic; Female; Fibromyalgia; Humans; Hyperalgesia; Male; Middle Aged; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Pain Threshold

To determine whether the functional impairment seen in chronic fatigue syndrome (CFS) is associated with reduced levels of central opioids and/or deficiency of the hypothalamic-pituitary-adrenal (HPA) axis.. Single-blinded case-control study measuring functional and psychological status, basal hormonal parameters and ACTH/cortisol response to naloxone and ovine corticotrophin-releasing hormone (oCRH) vs. placebo in people with CFS and healthy controls.. Twelve people with CFS and 11 age-matched controls.. Hormonal parameters: basal levels of 09:00 h plasma cortisol, dehydroepiandrosterone sulfate (DHEAS) and IGF-1. 24-h urinary free cortisol. Plasma ACTH and cortisol response to naloxone 125 microg/kg, oCRH 1 microg/kg and placebo (normal saline). Psychological parameters: SF-36, Hamilton Depression Score, Hospital Anxiety and Depression Scale and Fatigue Scale.. There were highly significant differences between the CFS subjects and the controls with respect to the measures of fatigue and physical functioning. However, there were no differences in basal levels of 09:00 h cortisol (367 +/- 37 vs. 331 +/- 39 nmol/l, P = 0.51), DHEAS (4.2 +/- 0.6 vs. 4.0 +/- 0.5 micromol/l, P = 0.81), 24-h urinary free cortisol (182 +/- 27 vs. 178 +/- 21 nmol/24 h, P = 0.91) or IGF-1 (145 +/- 19 vs. 130 +/- 11 microg/l, P = 0.52) between the CFS group and controls, respectively. There was also no difference between the groups with respect to the ACTH and cortisol response to either oCRH or naloxone.. Our data do not support an aetiological role for deficiency in central opioids or the HPA axis in the symptoms of CFS.

Topics: Adrenocorticotropic Hormone; Case-Control Studies; Corticotropin-Releasing Hormone; Dehydroepiandrosterone Sulfate; Fatigue Syndrome, Chronic; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin-Like Growth Factor I; Naloxone; Opioid Peptides; Pituitary-Adrenal System; Psychological Tests; Single-Blind Method

Opioidergic pathways have an inhibitory regulatory influence on the hypothalamic-pituitary-adrenal axis (HPA) in man. Previous studies have suggested impairment of pituitary-adrenal activation in chronic fatigue syndrome (CFS). We, therefore, decided to investigate the extent of opioid inhibition of HPA activity in CFS as a possible explanation for the reputed HPA hypofunctioning in patients with CFS.. Thirteen patients with CFS, diagnosed according to CDC criteria, were compared with thirteen healthy subjects. Adrenocorticotropin (ACTH) and cortisol (CORT) responses were measured following the administration of the opiate antagonist naloxone.. Baseline ACTH and cortisol levels did not differ between the two groups. The release of ACTH (but not cortisol) was significantly blunted in the CFS subjects compared with controls.. Naloxone mediated activation of the HPA is attenuated in CFS. Excessive opioid inhibition of the HPA is thus an unlikely explanation for the HPA dysregulation in this disorder.

Topics: Adrenocorticotropic Hormone; Adult; Area Under Curve; Case-Control Studies; Chi-Square Distribution; Fatigue Syndrome, Chronic; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Naloxone; Narcotic Antagonists; Neural Pathways; Pituitary-Adrenal System; Receptors, Opioid