calcitonin and Pain

Osteoporosis is a systemic skeletal condition characterized by decreased bone strength with consequent increased susceptibility to bone fracture. Fragility fractures in osteoporosis are often painful and result in loss of quality of life and disability. Salmon calcitonin (SCT) is a natural hormone that may assist in the management of osteoporotic patients following fracture by reducing fracture risk and decreasing pain. SCT is an antiresorptive agent which has been shown to reduce the risk of vertebral fractures (by 36%) in postmenopausal women with osteoporosis and previous fractures, with a safety profile comparable to placebo over long-term use. Clinical evidence suggests that SCT (with either subcutaneous and intranasal delivery) is an analgesic for the acute pain following osteoporotic fracture. Pain relief with SCT occurs after 1 week or less of treatment. Associated with this pain relief, vertebral fracture patients receiving SCT have been observed to have earlier mobilization compared with those receiving a placebo. Both preclinical and clinical data suggest a central analgesic effect for SCT. The mechanism(s) by which SCT induces pain relief has (have) not been conclusively shown. Neither a direct receptor-mediated action nor an indirect endorphin-mediated effect can be ruled out.

Topics: Analgesics; Animals; Calcitonin; Controlled Clinical Trials as Topic; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Pain

To investigate the analgesic effect of nasal salmon calcitonin on the post-fracture period of distal radius fracture.. In this prospective randomized double-blind study, forty-one postmenopausal women with a recent distal radius fracture treated conservatively were randomly assigned to receive either 200 IU of intranasal salmon calcitonin or placebo daily for 3 months following fracture. The assessment of the patient's pain was recorded using the Visual Analogue Scale (VAS).. The average age of the calcitonin group was 67.11 (SD, ±8.68) years and 64.91 (SD, ±7.48) of the placebo group. In the calcitonin group, the mean VAS score improved from 4.05 to 0.53 while in the placebo group from 3.36 to 0.32. A higher decrease of VAS score during the first post-fracture period was observed in the calcitonin group.. In the study, there is a statistically significant calcitonin mediated analgesic effect in the immediate post fracture period (at 10 days) when compared to placebo group. These results are in accordance with literature referring to the analgesic effect of calcitonin in the acute osteoporotic vertebral compression fracture. Thus calcitonin administration could be recommended to a short term course in acute osteoporotic conservatively treated distal radius fractures.

Topics: Administration, Intranasal; Aged; Analgesics; Calcitonin; Double-Blind Method; Female; Humans; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Pain; Pain Measurement; Prospective Studies; Radius Fractures; Treatment Outcome

This study aimed to investigate calcitonin as an effective therapy for osteoporosis in patients with bone pain during the anastrozole treatment of breast cancer. Ninety-one patients, who were on anastrozole treatment for breast cancer and also suffered anastrozole-induced bone pain, were randomly divided into two groups: the calcitonin group received salmon calcitonin and Caltrate D, and the control group received Caltrate D. All patients were evaluated by the visual analogue scale (VAS) and underwent the dual energy x-ray absorptiometry test for bone mineral density (BMD), and serum osteocalcin (BGP), alkaline phosphatase (ALP), calcium (Ca), and phosphorus (P) were measured at three months before and after the treatment. Significant differences in serum Ca, P, BGP, and ALP were found in each group between before and after treatment (P < 0.05), while no differences between the calcitonin and control groups were found. No difference was observed in femur BMD between the two groups, or between before and after treatment in each group. There was a significant difference in spine BMD between before and after treatment in the control group (P < 0.05) but not in the calcitonin group, while no difference was found between the calcitonin and control groups. Futhermore, VAS score significantly declined in each group after treatment (P < 0.05), but much more in the calcitonin group than the control group (P < 0.05). Our finding suggests that calcitonin may alleviate bone pain during the anastrozole treatment of breast cancer but has no effect on bone loss during cancer treatment.

Topics: Absorptiometry, Photon; Aged; Alkaline Phosphatase; Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone Density; Bone Density Conservation Agents; Breast Neoplasms; Calcitonin; Calcium; Female; Femur; Humans; Middle Aged; Nitriles; Osteocalcin; Osteoporosis; Pain; Phosphorus; Spine; Triazoles

To evaluate the effects of oral salmon calcitonin (sCT) on Lequesne's algofunctional index scores and on biomarkers of joint metabolism in knee osteoarthritis.. In this randomized, double-blind trial, patients received either placebo (n = 18), 0.5 mg of sCT (n = 17), or 1 mg of sCT (n = 18) daily for 84 days. Biomarkers included C-telopeptide of type II collagen (CTX-II), type II collagen neoepitope C2C, collagenases (matrix metalloproteinase 1 [MMP-1], MMP-8, and MMP-13), stromelysin (MMP-3), tissue inhibitors of metalloproteinases 1 and 2, and hyaluronan. Statistical analysis included nonparametric tests.. A total of 41 patients completed the study (13 in the group receiving 0.5 mg of sCT and 14 in each of the other 2 other groups). Although, on day 84, patients in both the placebo group and the group receiving 1 mg of sCT exhibited a similar significant decrease in pain scores, a significant reduction in the function score was observed only in the 2 sCT groups. On day 84, there was no significant decrease in biomarker levels in the placebo group, whereas significant reductions in the levels of both MMP-3 and hyaluronan were observed in the 2 sCT groups. The group of patients receiving 1 mg of sCT exhibited significant decreases in the levels of CTX-II, C2C, and MMP-13.. By improving functional disability and by reducing levels of biomarkers that are thought to be predictive of joint space narrowing (and thus cartilage loss), oral sCT at a dose of 1 mg might be a useful pharmacologic agent in human knee OA.

Topics: Aged; Aged, 80 and over; Biomarkers; Calcitonin; Collagen Type II; Double-Blind Method; Female; Gene Expression Regulation; Humans; Hyaluronic Acid; Knee Joint; Male; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Middle Aged; Osteoarthritis, Knee; Pain; Severity of Illness Index; Treatment Outcome

This prospective nonrandomized trial was performed to evaluate the efficacy of salmon calcitonin (sCT) in controlling pain related to bone metastasis in cancer patients and the relation of sCT's analgesic efficacy with beta-endorphin blood levels. The study group consisted of 22 cancer patients with bone metastases (male 13 and female 9, age range 38-77 years). Pain control was first achieved by continuous subcutaneous (s.c.) morphine administration. The next increase in pain was managed with continuous s.c. administration of 400 IU/day sCT. Beta-endorphin blood levels were measured before and during sCT administration. The first measurement was taken before sCT administration; subsequent measurement occurred at 12, 24, and 48 hours and 7 days after the commencement of treatment. Pain scores were monitored by a visual analogue scale. A complete blood count and a biochemical screening profile were taken before the administration of calcitonin and also on the seventh and the fifteenth day of the administration. The results showed a satisfactory analgesic effect. The mean pain score before the calcitonin administration was 4.43 and the score on the seventh day was 1.17. The gradual reduction of pain score was associated with an increase in beta-endorphin blood levels (increase to 147.2% of baseline on the seventh treatment day). In three cases, no satisfactory analgesic effect was obtained and pain control was achieved by increasing the continuous s.c. morphine dosage. No significant side effects were observed. These data suggest that sCT in high doses may be a useful adjuvant analgesic when combined with low doses of morphine in continuous s.c. administration for the management of metastatic bone pain.

Topics: Adult; Aged; Analgesics; beta-Endorphin; Bone Neoplasms; Calcitonin; Dose-Response Relationship, Drug; Female; Humans; Injections, Subcutaneous; Male; Middle Aged; Pain; Prospective Studies

To evaluate the analgesic efficacy of calcitonin suppositories (200 IU) in comparison with bed rest and paracetamol tablets, as a rescue analgesic.. A prospective, double-blind, randomized, placebo-controlled, clinical trial.. Forty patients (8 men and 32 postmenopausal women), who had recently (within the last 5 days) suffered a nontraumatic osteoporotic vertebral fracture.. All patients were admitted to the hospital, divided randomly into two groups and received either one calcitonin or placebo suppository once a day, respectively, for 28 days. All patients were allowed to take paracetamol tablets (500 mg), with a maximum dose of six tablets daily.. Spinal pain evaluation was performed at the beginning of the study (before the initiation of treatment) and then daily until the end of the study (day 28) using the Huskinsson's visual analog scale (VAS) and a painmeter device, by direct pressure on the fractured vertebra. Pain was evaluated with the patients attempting or performing four different locomotor functions, e.g., bed rest, sitting, standing, and walking functions. Biochemical urine and plasma measurements were carried out before the initiation of treatment and on days 14 and 28.. All calcitonin-treated patients experienced an overall statistically significant (all p values < 0.001) decrease of spinal pain as assessed by the VAS and the painmeter device. Pain relief allowed for early mobilization and the gradual restoration of the locomotive functions in the calcitonin-treated group. Placebo-treated patients remained in bed for almost the whole of the observation period. At the end of the study (28th day), fasting osteocalcin, hydroxyproline/creatinine, and calcium/creatinine ratio values were statistically significantly (all p values < 0.001), lower in the calcitonin-treated than in the placebo-treated patients. In the placebo group these values showed a gradual increase. In the calcitonin-treated group side effects mainly included dizziness and enteric irritation caused by the suppositories. Enteric irritation was also present in the placebo-treated group.. Salmon calcitonin suppositories (200 IU daily) caused a dramatic decrease in spinal pain in patients with recent osteoporotic vertebral fractures and influenced the early mobilization and the gradual restoration of their locomotor functions.

Topics: Acute Disease; Aged; Aged, 80 and over; Analgesics; Calcitonin; Female; Humans; Male; Middle Aged; Osteoporosis; Pain; Pain Measurement; Placebos; Prospective Studies; Spinal Fractures; Suppositories; Walking

The aim of this study was to assess the efficacy and safety of nasal spray and subcutaneous formulations of salmon calcitonin. Two-hundred-four patients, 27 males and 177 females, aged 72 years on average, with a recent, painful, vertebral crush fracture were given either 50 IU/day of subcutaneous salmon calcitonin (SCSCT, 102 patients) or 200 IU/day of intranasal salmon calcitonin (INSCT, 102 patients) for 30 consecutive days, according to a double-blind, double-placebo design. The two-sided 95% confidence interval of the difference between the two formulations for the pain on D30 assessed by Huskisson's Visual Analogue Scale (VAS) [-5.3 mm, 7.9 mm] was included in the [-10 mm, 10 mm] reference interval. Equivalence of the two formulations, was demonstrated. At the end of the study, the 95% confidence intervals of VAS of both treatment groups were included in the [0 mm, 30 mm] interval, which is considered to be clinically pertinent. Relief was obtained in less than 10 days for more than 50% of patients. The urinary hydroxyproline/creatinine and calcium/creatinine ratios remained constant between D1 and D30 with both formulations. General safety was comparable between the two formulations. Local safety of INSCT was similar to that of its placebo.

Topics: Administration, Intranasal; Adult; Aerosols; Aged; Aged, 80 and over; Analgesics; Calcitonin; Calcium; Creatinine; Double-Blind Method; Female; France; Humans; Hydroxyproline; Injections, Subcutaneous; Longitudinal Studies; Male; Middle Aged; Pain; Spinal Fractures; Therapeutic Equivalency; Treatment Outcome

The effect of intranasal salmon calcitonin on pain, erosion progression, and bone loss in 40 women with rheumatoid arthritis was investigated. The study design was double blind, placebo controlled for the first four months and open for the next 36 months, allowing for cross over to active drug treatment or to the control group. Morning stiffness was reduced in the group treated with salmon calcitonin after two and four months. After an average follow up of 28 months no significant effect on erosion progression was observed using the Larsen score. The mean (SD) monthly progressions in the Larsen score in the calcitonin and control groups were 0.21 (0.22) and 0.23 (0.28) respectively. The bone mineral density was evaluated in the forearm and spine. During the 12 months of follow up the control group lost bone at a rate of 2%/year at the spine and 4.8%/year at the radius distal third. In contrast, the group receiving nasal calcitonin gained 1% in bone mineral density at the lumbar spine and no loss at the radius distal third. The increase in bone density at the spine in the calcitonin group was not sustained and a loss of 1.8%/year was observed in the second year. The difference with the placebo group remained significant.

Topics: Administration, Intranasal; Adult; Arthritis, Rheumatoid; Bone Density; Bone Resorption; Calcitonin; Double-Blind Method; Female; Follow-Up Studies; Humans; Middle Aged; Pain

Back pain due to vertebral collapse is the main symptom of postmenopausal osteoporosis. The clinical picture in these crush fractures varies, depending on the type and the location of fracture, but in general, a new vertebral crush fracture gives rise to severe pain that immobilizes the patient and necessitates bedrest. In this double-blind controlled clinical trial, 56 patients who had recently (within the last 3 days) suffered an osteoporotic vertebral fracture were hospitalized for a period of 14 days. Salmon calcitonin (100 IU) or placebo injections were given daily. Pain was rated daily on a 10-point scale by the same observers. Blood and urinary parameters were also evaluated. The results showed a significant (P less than 0.001) difference in pain intensity between the calcitonin group and the placebo group. This beneficial effect was generally apparent from the second day of treatment onward, and over the following 2 weeks, the patients were able to sit and stand, and gradually started to walk again. A significant decrease in urinary hydroxyproline and urinary calcium was also noted in the calcitonin group. It is concluded that calcitonin exerts a beneficial effect on back pain following a vertebral crush fracture.

Topics: Aged; Analgesics; Calcitonin; Calcium; Double-Blind Method; Female; Humans; Hydroxyproline; Osteoporosis, Postmenopausal; Pain; Spinal Fractures

Salmon calcitonin 100 MRCU/day or a saline placebo were given in daily injections for at least three months to 49 patients with bone metastases from breast cancer in a randomized double-blind trial. All patients were normocalcemic, and most patients had stable or regressing disease at start of trial. No improvement in general performance or bone pain was detected as measured by a visual analogue scale, the daily duration of pain or consumption of analgetic drugs. Calcitonin had no effect on disease progression as judged by bone scans and radiographs. Calcitonin therapy did not affect serum calcium, alkaline phosphatase, bone gla-protein, or the urinary excretion of calcium and hydroxyproline. Serum phosphate and magnesium decreased significantly during calcitonin treatment (p = 0.01, and 0.00005, respectively). It was concluded that salmon calcitonin in this dosage has no discernible effect on skeletal pain, general performance, bone metabolism or disease progression in patients with breast cancer metastatic to bone. A significant decrease in serum phosphate and magnesium probably indicated an effect of calcitonin on the renal excretion of these ions.

Topics: Bone Neoplasms; Breast Neoplasms; Calcitonin; Clinical Trials as Topic; Double-Blind Method; Electrolytes; Female; Humans; Pain; Random Allocation

The effects of salmon calcitonin administered 100 IU i.m. daily for 30 consecutive days were evaluated in patients with painful bone metastasis secondary to different types of solid cancer. The results were compared with placebo-receiving patients. In the 22 patients treated with calcitonin a significant reduction ( p less than 0.001) was observed in the severity of bone pain. Significant reductions were also encountered in the serum alkaline phosphatase (p less than 0.02) and urinary hydroxyproline excretion values (p less than 0.05) in calcitonin-treated patients, indicating an inhibition of bone destruction. It is concluded that salmon calcitonin has an important place in the treatment of patients with metastatic bone lesions both as a potent analgesic and as an effective inhibitor of bone destruction.

Topics: Adult; Aged; Alkaline Phosphatase; Bone Neoplasms; Calcitonin; Calcium; Female; Follow-Up Studies; Humans; Hydroxyproline; Male; Middle Aged; Pain; Time Factors

Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction when administered alone. KBPs (Key Bioscience peptides) are synthetic peptides based on salmon calcitonin and are expected to inhibit bone resorption and to be chondroprotective. In this study, we investigated if combining a standard of care NSAID (naproxen) with a KBP resulted in improvement in pain scores, as well as disease activity and structural damage in a rat model of RA.. Collagen-induced arthritis (CIA) was induced in 40 female Lewis rats by immunization with porcine type II collagen; 10 rats were given sham injections. CIA rats were treated with KBP and/or naproxen. Health scores and joint scores were evaluated daily. Mechanical and cold allodynia tests and burrowing tests were used to assess pain-like behaviors. Blood samples were collected for biomarker testing, and paws were collected for histology and microcomputed tomography.. Naproxen monotherapy increased the time until humane endpoints was reached, and improved health score, pain assessments, and trabecular thickness, while KBP monotherapy did not result in improvements. Combination therapy had improved efficacy over naproxen monotherapy; combination therapy resulted in improved health scores, and importantly reduced mechanical and cold allodynia assessment. Furthermore, protection of articular cartilage structure and preservation of bone structure and bone volume were also observed.. This study demonstrates that combining KBP and naproxen may be a relevant therapeutic strategy for RA, resulting in improvements to the overall health, pain, inflammation, and joint structure.

Topics: Amylin Receptor Agonists; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Bone Density Conservation Agents; Calcitonin; Collagen Type II; Disease Models, Animal; Female; Humans; Islet Amyloid Polypeptide; Naproxen; Pain; Pain Measurement; Rats, Inbred Lew; Receptors, Calcitonin; Swine

The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo meningeal preparations in rats. Rats were intraperitoneally administered saline, GTN (10 mg/kg), vehicle, saline + GTN, SC (50 μg/kg) + GTN, and SC alone. Also, ex vivo meningeal preparations were applied topically 100 μmol/L GTN, 50 μmol/L SC, and SC + GTN. Calcitonin gene-related peptide (CGRP) contents of plasma, trigeminal neurons and superfusates were measured using enzyme-immunoassays. Dural mast cells were stained with toluidine blue. c-fos neuronal activity in trigeminal nucleus caudalis (TNC) sections were determined by immunohistochemical staining. The results showed that GTN triggered the increase in CGRP levels in plasma, trigeminal ganglion neurons and ex vivo meningeal preparations. Likewise, GTN-induced c-fos expression in TNC. In in vivo experiments, GTN caused dural mast cell degranulation, but similar effects were not seen in ex vivo experiments. Salmon calcitonin administration ameliorated GTN-induced migraine pain by reversing the increases induced by GTN. Our findings suggested that salmon calcitonin could alleviate the migraine-like pain by modulating CGRP release at different levels including the generation and conduction sites of migraine pain and mast cell behaviour in the dura mater. Therefore salmon calcitonin may be a new therapeutic choice in migraine pain relief.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Cell Degranulation; Dura Mater; Gene Expression Regulation; Male; Mast Cells; Migraine Disorders; Pain; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Trigeminal Ganglion

Amylin is a member of calcitonin or calcitonin gene-related peptide (CGRP) family. Immunohistochemical study revealed a dense network of amylin-immunoreactive (irAMY) cell processes in the superficial dorsal horn of the mice. Numerous dorsal root ganglion (DRG) and trigeminal ganglion cells expressed moderate to strong irAMY. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed amylin receptor mRNA in the mouse spinal cord, brain stem, cortex, hypothalamus and hippocampus. The nociceptive or antinociceptive effects of amylin were evaluated in the acetic acid-induced writhing test. Amylin (0.1, 0.5 and 1 mg/kg, intraperitoneally (i.p.) or 1-10 microg, intrathecally (i.t.)) reduced the number of writhes in a dose-dependent manner. Pretreatment of the mice with the amylin receptor antagonist salmon calcitonin (8-32), either by i.p. or i.t., antagonized the effect of amylin on acetic acid-induced writhing test. Locomotor activity was not significantly modified by amylin injected either i.p. (0.01-1 mg/kg) or i.t. (1-10 microg). Measurement of c-fos mRNA by RT-PCR or proteins by Western blot showed that the levels were upregulated in the spinal cord of mice injected with acetic acid and the increase was attenuated by pretreatment with amylin (10 microg, i.t.). Collectively, our result demonstrates that irAMY is expressed in DRG neurons with their cell processes projecting to the superficial layers of the dorsal horn, and that the peptide by interacting with amylin receptors in the spinal cord may be antinociceptive.

Topics: Acetic Acid; Amyloid; Analgesics; Animals; Brain; Calcitonin; Dose-Response Relationship, Drug; Ganglia, Spinal; Intracellular Signaling Peptides and Proteins; Islet Amyloid Polypeptide; Locomotion; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Pain; Proto-Oncogene Proteins c-fos; Receptor Activity-Modifying Proteins; Receptors, Calcitonin; Receptors, Islet Amyloid Polypeptide; Receptors, Peptide; RNA, Messenger; Spinal Cord; Viscera

Calcitonin (CT) is a peptide hormone produced by the parafollicular cells of the thyroid gland in mammals and by the ultimobranchial gland of birds and fish. Salmon calcitonin (sCT), which is more potent and longer lasting than human CT, has been used widely for the treatment of osteoporosis, paget's disease, hypercalcemic shock and chronic pain in terminal cancer patients. sCT is one of the many bioactive peptides that require C-terminal amidation for full biological activity. In this study we describe the over-expression and over-production of C-terminal amidated sCT in recombinant Streptomyces avermitilis. With this approach the utilization of expensive peptide synthesis can be circumvented.

Topics: Amino Acid Sequence; Analgesics; Animals; Calcitonin; DNA, Complementary; Molecular Sequence Data; Pain; Plasmids; Protein Processing, Post-Translational; Recombinant Proteins; Sequence Alignment; Streptomyces; Thyroid Gland

The aim of this paper is to study the influence of salmon calcitonin (SCT) on opioid analgesia when opioid transduction pathways are functionally uncoupled from Gi/o proteins by treatment with pertussis toxin (PTX). The antinociceptive effect of morphine and three selective opioid agonists, [D-Ala2,N-Me-Phe2,Gly5-ol]enkephalin (DAMGO) (OP(3-mu receptor agonist), [D-Pen2.5]-enkephalin (OP-1-delta receptor agonist) and trans-( +/- )-3,4-dichloro-N-methyl-N-[2-1(-pyrrolidinyl)-cyclohexyl]-benzene-acetam ide methane sulfonate (U-50, 488H) (OP1-kappareceptor agonist) was evaluated, using the tail flick test, in mice treated with PTX or with PTX and SCT. PTX blocked the antinociceptive effect of the opioids, being the antinociception similar in control animals and in mice treated with PTX and SCT. Thus, SCT prevents the effect of the blockade of Gi/o-proteins. From this it could be suggested that calcitonin activates alternative antinociceptive mechanisms that are not dependent on Gi/o-proteins.

Topics: Analgesia; Analgesics; Analgesics, Opioid; Animals; Calcitonin; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; GTP-Binding Proteins; Male; Mice; Morphine; Pain; Pertussis Toxin; Receptors, Opioid; Uncoupling Agents; Virulence Factors, Bordetella

We have examined the effects of salmon calcitonin (SCT), injected into the cerebral ventricle (i.c.v.), on the tail-biting and scratching behavior induced by the intrathecal injection of different types of nociceptive agents, i.e., substance P, N-methyl-D-aspartate (NMDA), kainate (KA), and quisqualate (Quis). Tail-biting and scratching behavior induced by the 4 substances was significantly inhibited by SCT (i.c.v.) in the same manner: the dose-response curves were U-shaped, and the most effective dose was 0.1 IU/mouse in all cases. SCT did not, however, completely inhibit tail-biting and scratching behavior. At its most effective dose, the percent inhibition of substance P-, NMDA-, KA- and Quis-induced behavior were 77.9%, 40.2%, 49.4%, and 52.9%, respectively. These results suggest that SCT has the inhibitory effects of substance P- and glutamate receptor agonists-induced nociceptive response in vivo.

Topics: Afferent Pathways; Animals; Calcitonin; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Injections, Intraventricular; Injections, Spinal; Kainic Acid; Male; Mice; N-Methylaspartate; Pain; Pain Measurement; Quisqualic Acid; Receptors, Glutamate; Receptors, Neurokinin-1; Spinal Cord; Substance P; Tail

Although the pain-relieving activity of salmon calcitonin has been mainly demonstrated for painful bone metastases it has been postulated that the drug possesses a central analgesic activity which is independent of the opiate receptor system. Thus, 16 patients with neuropathic cancer pain due to radicular compression by extraskeletal metastases, and without the possibility of any specific anticancer treatment, entered the study. Of the 16, 11 were pretreated with opiate-type analgesics. Salmon calcitonin was applied once daily at a dose of 200 IU in 500 ml 0.9% NaCl infused over 1 h. The total duration of the treatment was 20 days. The pain-relieving effect was classified as very good, good, moderate and bad; in 10 patients it was described as bad, in 2 as moderate in 2 as good and in 2 as very good. The drug failed in 9/11 opiate-pretreated patients. It is suggested that salmon calcitonin pain-relieving activity might depend on the tumor type, previous pain-relieving drug intake and site of metastatic disease.

Topics: Administration, Intranasal; Analgesics; Calcitonin; Drug Evaluation; Drug Monitoring; Humans; Infusions, Intravenous; Lymphatic Metastasis; Nerve Compression Syndromes; Pain; Pain Measurement; Pilot Projects; Retroperitoneal Neoplasms; Spinal Nerve Roots; Treatment Failure

We investigated whether the anti-aversive effects of salmon calcitonin (SCT) was induced by increasing ACTH and beta-endorphin and/or by decreasing of prostaglandin E2 (PGE2) levels in plasma of mice to elucidate the mechanisms responsible for the analgesic effects of SCT. Intracerebroventricular (i.c.v.) injections of SCT inhibited acetic acid-induced aversive behavior (writhing) in a U-shaped dose response curve, the most effective dose being 0.1 IU/mouse. Intraperitoneal (i.p.) injections of acetic acid increased, but not significantly, the levels of plasma ACTH and PGE2, but not beta-endorphin, which are considered to be psychoneuroendocrines correlated with pain. SCT (0.1 IU/mouse, i.c.v.) significantly increased plasma ACTH levels (p < 0.05) and tended to increase beta-endorphin levels (p = 0.052) in acetic acid-treated mice, whereas no change in PGE2 level was observed (p > 0.1). These results suggest that the anti-aversive effects of SCT may be mediated, at least in part, by the activation of ACTH.

Topics: Acetates; Acetic Acid; Adrenocorticotropic Hormone; Analgesics; Animals; beta-Endorphin; Calcitonin; Dinoprostone; Male; Mice; Pain; Radioimmunoassay

We studied 21 women with postmenopausal osteoporosis, treated with salmon calcitonin nasal spray (100 IU/daily) and calcium (1 g/daily) for six months. Bone mineral content (BMC), measured before and at the end of therapy with lumbar dual photon absorptiometry, showed a significant increase (p < 0.01). At the end of the study, there was also a clear improvement of osteoporotic pain. Among biochemical markers of bone turnover, there was a significant (p < 0.01) reduction of urinary excretion of hydroxyproline. No side effect was registered and all patients had a good compliance to therapy.

Topics: Absorptiometry, Photon; Administration, Inhalation; Aerosols; Bone and Bones; Calcitonin; Calcium; Female; Humans; Hydroxyproline; Middle Aged; Osteoporosis, Postmenopausal; Pain

Experimental and clinical evidence testifies to an antinociceptive action of salmon calcitonin (sCT), administered in different ways, on the central nervous system. These studies were performed almost exclusively in acute pain models. The purpose of the present study was to investigate the effects of sCT, injected directly into the lateral cerebral ventriculi, on the firing of single nociceptive thalamic neurons, detected by electrophysiological techniques in an experimental model of prolonged or chronic pain, such as rats rendered arthritic by injection of Freund's adjuvant into the left hindfoot. The noxious test stimuli used were either extension or flexion of the ankle or mild lateral pressure on the heel. With increasing doses of sCT (5, 10, 20, 40 micrograms, 5 microliters/i.c.v.) it was possible to observe correspondingly increasing inhibitory and long-lasting effects on the evoked firing, with a significant dose-effect relationship. In agreement with electrophysiological findings, preliminary data, obtained with a patch clamp technique, on depression of calcium fluxes through neuronal membrane, induced by sCT, oriented the attention to a direct action of sCT on CNS.

Topics: Analgesics; Animals; Arthritis, Experimental; Calcitonin; Chronic Disease; Disease Models, Animal; Electrophysiology; Injections, Intraventricular; Male; Movement; Nociceptors; Pain; Physical Stimulation; Pressure; Rats; Rats, Sprague-Dawley; Thalamus

We identify a new syndrome of acquired painful diffuse osteosclerosis associated with past intravenous drug abuse in two adults.. A 28-year-old white woman and a 38-year-old black man with a history of non-A, non-B chronic active hepatitis were referred to us for increasing bone pain that was especially severe in their lower extremities. They were studied at our clinical research center.. Skeletal radiographs documented progressive generalized osteosclerosis. Increased bone mass was confirmed by dual-energy radiography, and bone scintigraphy showed diffusely increased radionuclide accumulation. Serum biochemical studies revealed elevated alkaline phosphatase activity and osteocalcin levels, mild to moderately increased 1,25-dihydroxyvitamin D concentrations, and normal parathyroid hormone levels. In urine, hydroxyproline excretion was elevated, whereas calcium levels were reduced. Iliac crest histomorphometry showed increased rates of bone formation. Hematology, renal function, serum protein electrophoresis, and screening for fluorosis as well as vitamin A and heavy metal poisoning were all normal. Family histories were negative. Both patients were seropositive for antibody against hepatitis C virus as well as against Epstein-Barr virus (antiviral capsid antigen IgG but not IgM). Each subject was seronegative for cytomegalovirus, human immunodeficiency virus (HIV) 1 and 2, and human T-cell lymphotropic virus (HTLV) 1 and 2. Assay for reverse transcriptase in lymphocyte co-culture fluid and polymerase chain reaction studies using HIV-1 primers on peripheral monocyte DNA were negative. Treatment with synthetic salmon calcitonin in both individuals rapidly led to decreased bone pain and to a decline in biochemical parameters of accelerated bone turnover.. Painful diffuse osteosclerosis can follow intravenous drug abuse and is possibly caused by parenteral transmission of a virus that in some way stimulates bone formation.

Topics: Adult; Antibodies, Viral; Bone Remodeling; Calcitonin; Female; Hepacivirus; Herpesvirus 4, Human; Humans; Immunoglobulin G; Male; Osteosclerosis; Pain; Radiography; Substance Abuse, Intravenous

Calcitonin has been observed to have an analgesic effect on painful bone conditions. A case illustrating the antinociceptive effect of calcitonin on bone pain caused by osteoporotic vertebral compression fracture is presented. There is increasing clinical evidence supporting this phenomenon, though few rigorously controlled studies exist. Calcitonin may have an advantage over other analgesics in the treatment of bone pain resulting from an osteoporotic compression fracture, because, in addition to the observed analgesic effect, it is useful in treating the underlying disorder.

Topics: Aged; Analgesics; Calcitonin; Female; Humans; Osteoporosis, Postmenopausal; Pain; Spinal Fractures; Thoracic Vertebrae

Twenty-four women (mean age +/- SD 49 +/- 13 years) with classical or definite rheumatoid arthritis (disease duration 15 +/- 8 years) were treated with synthetic salmon calcitonin (SCT) nasal spray 200 IU three times a week for 3 months. Bone biopsies from the iliac crest were taken before and after SCT treatment. Histomorphometrical quantification of undecalcified bone sections was made using the manual point-counting method. SCT decreased the resorption surface of trabecular bone (ES/BS) significantly (P less than 0.001). There was also a significant increase (P less than 0.05) in trabecular bone volume (BV/TV) after 3 months of treatment, whereas no statistically significant changes were found in osteoid parameters. There were no significant changes in biochemical analyses of bone metabolism. We conclude that SCT might be useful in the prevention of bone loss in RA.

Topics: Adult; Arthritis, Rheumatoid; Bone and Bones; Bone Resorption; Calcitonin; Female; Humans; Middle Aged; Pain

Topics: Animals; Calcitonin; Pain; Rats

We determined the effects on nociceptive threshold and motor function of dynorphin-gene products, dynorphin A-(1-32) (DYN A-(1-32), DYN A-(1-8), DYN B and DYN B-29 and the non-opioid peptides somatostatin, neurotensin and salmon calcitonin (s-CT) after intrathecal administration in the rat. DYN A-(1-32) (25 nmol) produced maximal elevation of tail-flick latency accompanied by severe hind limb paralysis and tail flaccidity lasting 6 h and still present at 24 h in several animals. Antinociception evaluated by the vocalization test wore off within 2 h. A lower dose of the peptide (6.25 nmol) did not alter the tail-flick reflex and motor function but significantly elevated the vocalization threshold. The other dynorphins showed weaker, short-lasting activity on the nociceptive threshold, the order of potency being as follows: DYN B-29 greater than DYN B greater than DYN A-(1-8). On the other hand, at the high doses DYN B (100 nmol) and DYN B-29 (50 and 100 nmol) caused moderately severe hind limb paralysis whereas DYN A-(1-8) did not cause any motor impairment up to the dose of 100 nmol. MR 1452, a relatively preferential antagonist of the kappa opioid receptor, prevented both the antinociceptive and motor effects of dynorphins. Intrathecal somatostatin (25 nmol) had a profile of activity superimposable on that of DYN A-(1-32): long-lasting (up to 24 h) elevation of tail-flick latency with hind limb paralysis, and a shorter (4 h) elevation of the vocalization threshold. MR 1452 did not modify these effects. Intrathecal neurotensin (25 nmol) and s-CT (0.5 nmol) did not alter tail-flick latency or vocalization threshold. However, adopting the hot plate as the analgesimetric test, both peptides elevated the time of hind paw licking, taken as an index of nociception. No signs of motor dysfunction were observed at the doses employed.

Topics: Animals; Calcitonin; Dynorphins; Injections, Spinal; Male; Movement; Neurotensin; Nociceptors; Pain; Rats; Rats, Inbred Strains; Somatostatin; Time Factors

Topics: Adult; Aged; Bone and Bones; Bone Neoplasms; Calcitonin; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Radionuclide Imaging

Topics: Arthritis; Calcitonin; Drug Administration Schedule; Humans; Osteoporosis; Pain