Pain
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Expression of bradykinin receptors was analyzed in freshly isolated dorsal root ganglion neurons of the ipsi- and contralateral segments L4/L5, L2/L3, and T12/T13 two to twenty days after unilateral injury of the adult rat sciatic nerve using gold labeled bradykinin. The number of infiltrating leucocytes was investigated by flow cytometry. Sciatic nerve injury transiently increased the proportion of neurons expressing bradykinin receptors not only in the ipsilateral ganglia L4/L5, but also in the homonymous contralateral ganglia and also bilaterally in the adjacent ganglia L2/L3. ⋯ No increase was observed prior to day ten and only in ipsilateral ganglia L4/L5, not contralaterally and not in adjacent ganglia L2/L3 and T12/T13. The experiments show that the induction of bradykinin receptors following a unilateral nerve lesion is not restricted to neurons projecting into the damaged nerve but is (i) bilateral, (ii) different in time course between injured and uninjured neurons, and (iii) locally confined to neurons of the adjacent ganglia. Macrophages and lymphocytes are increased after ten day ligation only in the affected ganglia and are probably not involved in the induction of bradykinin receptors.
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Pain intensity ratings of 'usual' pain, or pain 'on average', are gaining in popularity since they are arguably a more realistic measure of a patient's pain status than the single snapshot of 'current' pain. An alternative to the 'actual average' of ratings obtained from multiple measures is the single rating of patients' recall of their 'usual' pain over a period of time, usually 1 week. The use of such a scale relies on the assumption that patients can accurately recall their 'usual' pain. ⋯ Using the Intra-class Correlation Coefficient (ICC) to compute accuracy, the single rating asking patients to estimate their pain 'on average' over the week was found to be an accurate measure of 'actual average' pain intensity (ICC=0.82) and more accurate than 'current' pain (ICC=0.66). Although some composite measures of single ratings gave more accurate estimates of 'actual average' pain, this was not considered sufficient advantage to advocate their use. The results of this study propose the single rating of pain 'on average' as a valid and practical measure of a patient's pain intensity over a period of 1 week.
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The development of tolerance following repeated doses of morphine hinders the treatment of clinical pain. We have previously shown that morphine tolerance develops in neuropathic rats without cross-tolerance to a systemic kappa-opioid agonist; in the current work, using paw-pressure vocalization thresholds, we studied the antinociceptive effect of the peripherally-selective kappa (kappa)-opioid agonist, asimadoline, in both morphine-tolerant and opioid-naïve rats 2 weeks after sciatic nerve injury. In naïve rats, intraplantar (i.pl.) injection of asimadoline into the nerve-injured paw, at doses of 10, 15 and 20 (but not 30) microg, dose-dependently relieved the mechanical allodynia-like behaviour. ⋯ These results confirm that at low doses, asimadoline exerts its action only in the periphery. In morphine-tolerant rats (after 10 mg/kg s.c. , twice daily for 4 days) and naïve, saline-pretreated rats, asimadoline (15 microg, i.pl.) relieved the mechanical allodynia-like behaviour to the same extent, indicating no cross-tolerance between morphine and the peripherally-selective drug. Our findings show promise for the treatment of neuropathic pain with low doses of peripherally-selective kappa-opioids.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Prediction of physician visits and prescription medicine use for back pain.
The primary purpose of this study was to examine the extent to which specific patient attitudes and beliefs about medical care and self-care for back pain predict future healthcare use. An automated database allowed examination of the predictive relationships in two primary care patient samples. In general, beliefs that physicians should find a definitive cause and permanent cure for back pain predicted neither physician visits nor prescription medication fills. ⋯ Factor analyses of the item set yielded three factors, but inconclusive results; the internal consistency of the identified sub-scales was only moderate. However, findings that a subset of items predicted physician visits and prescriptions medication fills, and was sensitive to change following a self-care intervention, suggest avenues for improving measurement of self-care orientation. These findings help clarify specific patient attitudes and beliefs that are related to healthcare utilization and suggest that a subset of these beliefs can be modified through a brief educational intervention.
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Clinical Trial Controlled Clinical Trial
The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain.
Nalbuphine, pentazocine, and butorphanol, mixed agonist/antagonist opioids that induce analgesia by acting predominantly at kappa opioid receptors, have recently been shown in single-dose studies to have greater analgesic efficacy in women than in men. In the current experiments, the first placebo controlled dose response study of opioid analgesic efficacy that examines for gender differences, nalbuphine (5, 10, or 20 mg) and placebo were evaluated in 62 men and 69 women for the treatment of moderate to severe postoperative pain following extraction of impacted wisdom teeth. In a randomized, open injection, double blind experimental design, pain intensity was recorded on a 10 cm visual analog scale (VAS) immediately prior to drug administration (baseline) and at 20 min intervals thereafter. ⋯ These results suggest that the optimal analgesic dose of nalbuphine for women is lower than the highest dose that can be safely administered. In contrast, the antianalgesic effect of nalbuphine suggests avoidance of its routine use for postoperative analgesia in men until further studies clarify this issue. Because gender differences in other mixed kappa agonists/antagonists (i.e. pentazocine and butorphanol) have previously been shown, these results may generally apply to this class of opioid analgesics.