Pain
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Comparative Study
Spinal and local peripheral antiallodynic activity of Ro64-6198 in neuropathic pain in the rat.
The nociceptin system seems to be involved in modulation of acute nociceptive stimulation and in chronic pain processes, e.g. inflammation and neuropathy. In the present study, we examined the analgesic effect of a new opioid receptor-like (ORL1) receptor agonist, Ro64-6198, and compared it with the effect of endogenous ORL1 receptor agonist, nociceptin/orphanin FQ (N/OFQ), in a model of neuropathic pain in the rat. Ro64-6198 was injected intrathecaly (i.t.), intraplantarly (i.pl.) and subcutaneously (s.c.), and responses of neuropathic rats were measured in tactile (von Frey) and thermal (cold water) allodynia tests. ⋯ Moreover, the observed antiallodynic potency of Ro64-6198 was weaker in comparison with N/OFQ after i.t. administration of either agonist, but almost equal after i.pl. injection. Selective antagonists of the ORL1 receptor, [Phe1Psi(CH2-NH)Gly2]NC(1-13)NH2 (PhePsi) and [N-Phe1]-NC(1-13)NH2 (NPhe), inhibited the antiallodynic actions of Ro64-6198 which indicated that the spinal and peripheral antinociceptive effects were mediated by ORL1 receptors. Therefore, besides spinal, also peripheral ORL1 receptors may be targeted by drugs designed for the long-term treatment of chronic pain.
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Comparative Study
A rat model of unilateral hindpaw burn injury: slowly developing rightwards shift of the morphine dose-response curve.
Management of pain after burn injury is an unresolved clinical issue. In a rat model of hindpaw burn injury, we examined the effects of systemic morphine on nociceptive behaviors following injury. Injury was induced by immersing the dorsal part of one hindpaw into a hot water bath (85 degrees C) for 4, 7, or 12 s under pentobarbital anesthesia. ⋯ In both injured and sham rats, the anti-nociceptive effects of subcutaneous morphine were examined on post-injury days 7 and 14. While the morphine AD50 dose was comparable on day 7 between burn (1.61 mg/kg) and control (1.7 mg/kg) rats, the morphine dose-response curve was shifted to the right in burn-injured rats (4.6 mg/kg) on post-injury day 14 as compared with both the injured rats on post-injury day 7 and sham rats on day 14 (1.72 mg/kg). These data indicate that hindpaw burn injury reliably produces persistent mechanical allodynia and thermal hyperalgesia and that the reduced efficacy of morphine anti-nociception in chronic burn injury may be in part due to a downregulation of spinal mu-opioid receptors.
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Trial methodology was evaluated in paediatric analgesic studies. Databases were searched for randomised, placebo controlled studies of systemic paracetamol, NSAIDs and opioids administered for acute postoperative pain in children. Eighty-three studies met the inclusion criteria and 40 were included for the analysis. ⋯ Most patients in the placebo groups had pain that was greater than 30% of the maximum. In conclusion, analysis of the methodology showed several aspects of trial design that can be improved in future studies. Placebo control groups can be used in paediatric analgesic studies to demonstrate internal sensitivity.
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Randomized Controlled Trial Comparative Study Clinical Trial
Effects of a workplace physical exercise intervention on the intensity of headache and neck and shoulder symptoms and upper extremity muscular strength of office workers: a cluster randomized controlled cross-over trial.
The purpose of the study was to examine the effects of a workplace physical exercise intervention on the perceived intensity of headache and the intensity of symptoms in the neck and shoulders, as well as on the extension and flexion strength of the upper extremities. The study was a cluster randomized controlled trial. The cross-over design consisted of physical exercise intervention (15 weeks) and no-intervention (15 weeks). ⋯ The mean increase in the extension strength of the upper extremities was 1.3 kg (95% CI 0.5-2.1) (P=0.001) or 4% (95% CI 1-6). The intervention had no effect on the intensity of shoulder symptoms or the flexion strength of the upper extremities. Specific exercise may be clinically important to alleviate headache and neck symptoms.
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While it is well established that acute stress can produce antinociception, a phenomenon referred to as stress-induced analgesia, repeated exposure to stress can have the opposite effect. Since, chronic pain syndromes, such as fibromyalgia and rheumatoid arthritis, may be triggered and/or exacerbated by chronic stress, we have evaluated the effect of repeated stress on mechanical nociceptive threshold and inflammatory hyperalgesia. Using the Randall-Selitto paw pressure test to quantify nociceptive threshold in the rat, we found that repeated non-habituating sound stress enhanced the mechanical hyperalgesia induced by the potent inflammatory mediator, bradykinin, which, in normal rats, produces hyperalgesia indirectly by stimulating the release of prostaglandin E2 from sympathetic nerve terminals. ⋯ In addition, implants of epinephrine restored bradykinin-hyperalgesia in sympathectomized non-stressed rats, lending further support to the suggestion that increased plasma levels of epinephrine can sensitize primary afferents to bradykinin. These results suggest that stress-induced enhancement of inflammatory hyperalgesia is associated with a change in mechanism by which bradykinin induces hyperalgesia, from being sympathetically mediated to being sympathetically independent. This sympathetic-independent enhancement of mechanical hyperalgesia is mediated by the stress-induced release of epinephrine from the adrenal medulla.