Articles: hyperalgesia.
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J. Diabetes Complicat. · May 1999
Thermal, but not mechanical, nociceptive behavior is altered in the Zucker Diabetic Fatty rat and is independent of glycemic status.
This study investigated the possible link between developing hyperglycemia and mechanical and/or thermal hyperalgesia in the Zucker Diabetic Fatty (ZDF) rat. When normoglycemic (nonfasting blood glucose levels of 6 mM), 6-week-old ZDF rats were glucose intolerant compared to the nondiabetic Zucker lean control (ZL) rats, but there was no difference in their response to a noxious mechanical (paw pressure test) or thermal (hot plate) stimulus (mechanical nociceptive thresholds: ZDF 176.7+/-14.4 g, ZL 161.7+/-13.3 g; latencies to response to the thermal stimulus: ZDF 13.1+/-1.6 sec, ZL 16.7+/-1.5 sec). Blood glucose levels in untreated ZDF rats increased to 28.4+/-2.9 mM by 20 weeks of age, while ZDF rats treated with the insulin sensitizer, rosiglitazone, and ZL rats remained normoglycemic (< or =8 mM) throughout the study. ⋯ In contrast, the latency to response to the thermal stimulus increased with time in ZL rats, but remained constant in hyperglycaemic ZDF rats such that the difference reached significance by 9 weeks of age (ZDF 11.6+/-1.7 sec, ZL 21.8+/-2.7 sec, p<0.01) and is consistent with hyperalgesia in the ZDF phenotype. However, this difference was not moderated by maintaining normoglycaemia in rosiglitazone-treated ZDF rats (12.8+/-1.3 sec). Together, the data suggest that hyperglycemia does not play a central role in the development of hyperalgesia in the ZDF rat.
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Randomized Controlled Trial Clinical Trial
Effect of riluzole on acute pain and hyperalgesia in humans.
Riluzole modulates several transmitter systems which may be involved in nociception. Antinociceptive effects have been shown in animal studies, but there are no human data. ⋯ We used a randomized, double-blind, placebo-controlled design, and subjects received riluzole 100 mg or placebo for 2 days with a 14-day interval. The burns produced significant hyperalgesia, but riluzole had no acute analgesic effects in normal or hyperalgesic skin.
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Cholecystokinin-B receptor activation has been reported to reduce morphine analgesia. Neuropathic pain is thought to be relatively refractory to opioids. One possible mechanisms for a reduced effect of morphine on neuropathic pain is the induction of cholecystokinin in the spinal cord by nerve injury. The authors evaluated the role of the spinal cholecystokinin-B receptor on morphine analgesia in two rat neuropathic pain models: chronic constriction injury and partial sciatic nerve injury. ⋯ The effectiveness of morphine for thermal hyperalgesia after nerve injury depends on the type of nerve injury. The role of the cholecystokinin-B receptor in morphine analgesia in thermal hyperalgesia after nerve injury also depends on the type of nerve injury.
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We have recently reported a model of secondary hyperalgesia in which facilitation of the thermal nociceptive tail-flick reflex following topical mustard oil is largely dependent on descending influences from the rostral ventromedial medulla (RVM). The current study was designed to examine a potential role for excitatory amino acid receptors and nitric oxide in the RVM in modulating this hyperalgesia. Topical application of mustard oil (100%) to the lateral surface of the hind leg of awake rats produced a short-lived (60 min) facilitation of the tail-flick reflex that was dose-dependently attenuated by microinjection of the selective N-methyl-D-aspartate (NMDA) receptor antagonist APV (1-100 fmol) into the RVM. ⋯ The hyperalgesia produced by NMDA injection into the RVM was blocked by prior intra-RVM injection of either APV or L-NAME. These results support the notion that secondary hyperalgesia produced by mustard oil involves concurrent activation of dominant descending facilitatory, as well as masked inhibitory systems from the RVM. Additionally, the data suggest that descending facilitation involves activation of NMDA receptors and production NO* in the RVM, whereas inhibition involves activation of non-NMDA receptors in the RVM.
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Prolonged nociceptive input following peripheral injury results in hyperalgesia (enhanced response to a noxious stimulus), which is thought to occur as a consequence of sensitization of primary afferent nociceptors and enhanced excitability of spinal dorsal horn nociceptive neurons (central sensitization). Since there is often an expansion of hyperalgesia to tissue adjacent, and even distant from the site of injury (secondary hyperalgesia), it is thought that this phenomenon primarily involves mechanisms of central modulation/plasticity. In contrast, hyperalgesia observed at the site of tissue injury (primary hyperalgesia) involves peripheral mechanisms. ⋯ The effect of bilateral rostral medial medulla lesions produced by the soma-selective neurotoxin ibotenic acid was determined in three different models of cutaneous thermal hyperalgesia following peripheral inflammation: (i) intraplantar injection of carrageenan into the hindpaw (model of primary hyperalgesia); (ii) intra-articular injection of carrageenan/kaolin into the knee of the hind leg (model of secondary hyperalgesia); and (iii) topical application of mustard oil to the hind leg (model of secondary hyperalgesia). Compared with sham lesion animals, a bilateral lesion of the rostral medial medulla completely blocked thermal hyperalgesia in the two models of secondary hyperalgesia (intra-articular carrageenan/kaolin injection into the knee and topical mustard oil application to the hind leg), but was ineffective in blocking facilitation of the thermal paw withdrawal response in the model of primary hyperalgesia (intraplantar carrageenan injection into the hindpaw). These results suggest that primary and secondary hyperalgesia are differentially modulated in the CNS, and support the notion that descending nociceptive facilitatory influences from the rostral medial medulla significantly contribute to secondary, but not primary, hyperalgesia.