Articles: hyperalgesia.
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Anesthesia and analgesia · May 2002
Selective and long-lasting neural blockade with resiniferatoxin prevents inflammatory pain hypersensitivity.
Capsaicin can produce a selective and long-lasting neural blockade. Resiniferatoxin (RTX) is an ultrapotent vanilloid agonist with a unique spectrum of activities different from that of capsaicin. We sought to determine whether a single application of RTX to a peripheral nerve could completely prevent the long-lasting mechanical hyperalgesia caused by carrageenan injection. In rat experiments, RTX (0.001%) was administered percutaneously to the sciatic and saphenous nerves before the intraplantar injection of carrageenan. Responses to noxious mechanical (pressure on the paw) and thermal (hot plate) stimulations and changes in paw circumference were measured at various time intervals for 8 days after treatment. The administration of RTX resulted in mechanical and thermal hypoalgesia (for 2 and 8 days, respectively). Inflammatory hyperalgesia was completely prevented by the precarrageenan injection of RTX. Inflammatory enhancement of paw circumference was reduced by RTX (12.0 +/- 2.4 mm versus 6.9 +/- 3.4 mm, P < 0.005). We suggest that the selective nature of the effect of vanilloid agonists on nociception could provide an opportunity for prolonged neural blockade when early mobilization and/or preservation of protective sensation are required. ⋯ We report that an ultrapotent vanilloid agonist resiniferatoxin can provide a selective and long-lasting neural blockade. Applied to the sciatic and saphenous nerves, it completely prevented pain hypersensitivity caused by prolonged inflammatory process (injection of carrageenan into the paw).
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The sympathetic system (SNS) is considered to be a major component of the neurogenic contribution to inflammation and hyperalgesia. We have investigated the role of the SNS in the local inflammatory pain induced by intraplantar (i.pl) injections of bacterial endotoxin (ET). Treatment of rats with an alpha-adrenoceptor antagonist (phentolamine, 0.25-1 mg/kg, i.p.), a beta-adrenoceptor antagonist (propranolol, 1-10 mg/kg, p.o.) or a sympathetic neuron-blocking agent (guanethedine, 30 mg/kg, s.c.) resulted in a dose-dependent reduction of the thermal hyperalgesia induced by ET. ⋯ IL-1 beta was resistant to all of the sympatholytic treatments. We conclude that the SNS can contribute to the local inflammation and hyperalgesia following injection of ET. The resistance to sympatholytics shown by IL-1 beta, known to play a key role in the inflammatory cascade, suggests that ET can initiate inflammation and hyperalgesia independently of peripheral and central sympathetic mechanisms.
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Anesthesia and analgesia · May 2002
The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance.
Perioperative opioids increase postoperative pain and morphine requirement, suggesting acute opioid tolerance. Furthermore, opioids elicit N-methyl-D-aspartate (NMDA)-dependent pain hypersensitivity. We investigated postfentanyl morphine analgesic effects and the consequences of NMDA-receptor antagonist (ketamine) pretreatment. The rat nociceptive threshold was measured by the paw-pressure vocalization test. Four fentanyl boluses (every 15 min) elicited a dose-dependent (a) increase followed by an immediate decrease of the nociceptive threshold and (b) reduction of the analgesic effect of a subsequent morphine administration (5 mg/kg): -15.8%, -46.6%, -85.1% (4 x 20, 4 x 60, 4 x 100 microg/kg of fentanyl, respectively). Ketamine pretreatment (10 mg/kg) increased the fentanyl analgesic effect (4 x 60 microg/kg), suppressed the immediate hyperalgesic phase, and restored the full effect of a subsequent morphine injection. Fentanyl also elicited a delayed dose-dependent long-lasting decrease of the nociceptive threshold (days) that was prevented by a single ketamine pretreatment before fentanyl. However, a morphine administration at the end of the fentanyl effects restored the long-lasting hyperalgesia. Repeated ketamine administrations were required to obtain a complete preventive effect. Although ketamine had no analgesic effect per se at the dose used herein, our results indicate that sustained NMDA-receptor blocking could be a fruitful therapy for improving postoperative morphine effectiveness. ⋯ Fentanyl-induced analgesia is followed by early hyperalgesia (hours), acute tolerance to the analgesic effects of morphine, and long-lasting hyperalgesia (days). All these phenomena are totally prevented by repeated administrations of the NMDA-receptor antagonist, ketamine, simultaneously with fentanyl and morphine administration.
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Descending influences from the rostral medial medulla (RMM) contribute to secondary hyperalgesia in persistent inflammatory, neuropathic, and visceral pain models. The current study examined if descending inhibition or facilitation from the RMM modulates primary and secondary hyperalgesia after incision in the rat hind limb. ⋯ Primary and secondary hyperalgesia after an incision were not modulated by descending influence from the RMM. The lack of contribution of descending facilitatory influences from the RMM to secondary hyperalgesia after gastrocnemius incision supports the notion that incision-induced pain involves dissimilar mechanisms compared with inflammatory and neuropathic pain.
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Recent research has focused on prostaglandins in the central nervous system and their contribution to hyperalgesia and allodynia. This study sought to establish whether neurokinin-1 (NK-1) receptors and glutamate receptors are involved in the hyperalgesic and allodynic effects of spinally administered prostaglandin E2 (PGE2) in rats, and also to determine if the same receptors are involved the hyperalgesia induced by intraplantar administration of zymosan, an inflammatory agent which is known to evoke spinal PGE2 release. Spinal application of antagonists of the NK-1 receptor, the -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate or metabotropic glutamate receptor significantly attenuated the decrease in mechanical paw withdrawal response thresholds produced by either spinal administration of PGE2 or intraplantar administration of zymosan. ⋯ These results suggest that both PGE2-induced and zymosan-induced mechanical hyperalgesia are mediated in part through activation of NK-1, AMPA/kainate and metabotropic glutamate receptors. PGE2-induced, but not zymosan-induced, thermal hyperalgesia is mediated in part by activation of NMDA, AMPA/kainate and metabotropic glutamate receptors. Activation of both NMDA and AMPA/kainate receptors contribute to PGE2-induced allodynia.