Pain
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Comparative Study
Involvement of cholecystokinin in the opioid tolerance induced by dipyrone (metamizol) microinjections into the periaqueductal gray matter of rats.
The analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs) is partly due to an action upon the periaqueductal gray matter (PAG), which triggers the descending pain control system and thus inhibits nociceptive transmission. This action of NSAIDs engages endogenous opioids at the PAG, the nucleus raphe magnus and the spinal cord. Repeated administration of NSAIDs such as dipyrone (metamizol) and acetylsalicylate thus induces tolerance to these compounds and cross-tolerance to morphine. ⋯ In rats tolerant to PAG dipyrone, a PAG microinjection of proglumide restored the antinociceptive effect of a subsequent microinjection of dipyrone or morphine. These results suggest that PAG-microinjected dipyrone triggers and/or potentiates local opioidergic circuits leading to descending inhibition of nociception, on the one hand, and to a local antiopioid action by cholecystokinin, on the other. Reiteration of these events would then result in an enhancement of cholecystokinin's antiopioid action and thus tolerance to opioids and dipyrone in the PAG.
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A neuropathic-like pain syndrome was produced in rats following prolonged hindpaw ischemia and reperfusion, creating an animal model of complex regional pain syndrome-Type I (CRPS-I; reflex sympathetic dystrophy) that we call chronic post-ischemia pain (CPIP). The method involves placing a tourniquet (a tight fitting O-ring) on one hindlimb of an anesthetized rat just proximal to the ankle joint for 3 h, and removing it to allow reperfusion prior to termination of the anesthesia. Rats exhibit hyperemia and edema/plasma extravasation of the ischemic hindpaw for a period of 2-4 h after reperfusion. ⋯ The rats also exhibit spontaneous pain behaviors (hindpaw shaking, licking and favoring), and spread of hyperalgesia/allodynia to the uninjured contralateral hindpaw. Light-microscopic examination of the tibial nerve taken from the region just proximal to the tourniquet reveals no signs of nerve damage. Consistent with the hypothesis that the generation of free radicals may be partly responsible for CRPS-I and CPIP, two free radical scavengers, N-acetyl-L-cysteine (NAC) and 4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl (Tempol), were able to reduce signs of mechanical allodynia in this model.
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Tri-cyclic antidepressants (TCAs) have been widely used in treating major depressive disorders. Recent studies further demonstrated that TCAs have potent sodium channel blocking effect, and amitriptyline, one of the TCAs, has a potent spinal anesthetic effect. The aim of the study was to evaluate the spinal anesthetic effect of various TCAs and to see whether these TCAs could likewise act as local anesthetics after a single intrathecal injection. ⋯ Under this concentration, amitriptyline had a similar potency but longer duration of spinal blockade of motor, propioception, and nociception (P<0.001) than did bupivacaine, whereas several other TCAs had similar or less potencies of spinal blockade than did bupivacaine. In dose-response studies, amitriptyline had a more potent (P<0.005) and longer duration (P<0.001) of spinal blockade than did bupivacaine. We concluded that intrathecal amitriptyline had a more potent and longer duration of spinal anesthetic effect than did bupivacaine, whereas several other TCAs had similar or less potencies than did bupivacaine.
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Comparative Study
Pain related behaviour in two models of osteoarthritis in the rat knee.
Osteoarthritis (OA) is a major healthcare burden, with increasing incidence. Pain is the predominant clinical feature, yet therapy is ineffective for many patients. While there are considerable insights into the mechanisms underlying tissue remodelling, there is poor understanding of the link between disease pathology and pain. ⋯ Diclofenac and paracetamol were effective 3 days after arthritic induction only, coinciding with a measurable swelling of the knee. Gabapentin varied in its ability to reverse both hyperalgesia and allodynia. The iodoacetate model provides a basis for studies on the mechanisms of pain in OA, and for development of novel therapeutic analgesics.
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Comparative Study
Reduced heat sensitivity and epidermal nerve fiber immunostaining following single applications of a high-concentration capsaicin patch.
Capsaicin-containing plant extracts have been used as topical treatments for a variety of pain syndromes for many centuries. Current products containing capsaicin in low concentrations (usually 0.025-0.075% w/w) have shown efficacy against a variety of pain conditions in clinical studies. However, in order to produce significant analgesic effects, these formulations require frequent re-dosing, often as much as three to five times daily for several weeks. ⋯ The results show a significant reduction of heat, but not cold, sensitivity and reduction of ENF immunostaining with high-capsaicin concentration patch applications for 60 or 120 min, compared to placebo patch applications. Application sites exposed to low-capsaicin concentration (0.04%w/w) patches for 120 min or high-concentration patches for 30 min were not significantly different from placebo with respect to either thermal threshold detection or ENF immunostaining. The ability of a single 60 min high-concentration patch application to mimic effects produced by prolonged exposure to low-concentration capsaicin creams suggests a new approach to the management of chronic pain syndromes.