Articles: hyperalgesia.
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Anaesth Intensive Care · Feb 2005
ReviewHigh-dose buprenorphine: perioperative precautions and management strategies.
Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U. K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. ⋯ Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.
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Neurotrophin-3 (NT-3) negatively modulates nerve growth factor (NGF) receptor expression and associated nociceptive phenotype in intact neurons, suggesting a beneficial role in treating aspects of neuropathic pain mediated by NGF. We report that NT-3 is effective at suppressing thermal hyperalgesia associated with chronic constriction injury (CCI); however, NT-3 does not alter the mechanical hypersensitivity that also develops with CCI. Thermal hyperalgesia is critically linked to expression and activation of the capsaicin receptor, transient receptor potential vanilloid receptor-1 (TRPV1). ⋯ Exogenous NT-3 could both prevent the onset of thermal hyperalgesia and reverse established thermal hyperalgesia and elevated TRPV1 expression 1 week after CCI. Continuous infusion is required for suppression of both thermal hyperalgesia and TRPV1 expression, because removal of NT-3 resulted in a prompt reestablishment of the hyperalgesic state and corresponding CCI-associated TRPV1 phenotype. In conclusion, although NGF drives inflammation-associated thermal hyperalgesia via its regulation of TRPV1 expression, NT-3 is now identified as a potent negative modulator of this state.
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Opioid-induced hyperalgesia is characterized by hypersensitivity to innocuous or noxious stimuli during sustained opiate administration. Microinjection of lidocaine into the rostral ventromedial medulla (RVM), or dorsolateral funiculus (DLF) lesion, abolishes opioid-induced hyperalgesia, suggesting the importance of descending pain facilitation mechanisms. Here, we investigate the possibility that cholecystokinin (CCK), a pronociceptive peptide, may drive such descending facilitation from the RVM during continuous opioid administration. ⋯ These data suggest that activation of CCK2 receptors in the RVM promotes mechanical and thermal hypersensitivity and antinociceptive tolerance to morphine. Enhanced, endogenous CCK activity in the RVM during sustained morphine exposure may diminish spinal morphine antinociceptive potency by activating descending pain facilitatory mechanisms to exacerbate spinal nociceptive sensitivity. Prevention of opioid-dose escalation in chronic pain states by CCK receptor antagonism represents a potentially important strategy to limit unintended enhanced clinical pain and analgesic tolerance
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Comparative Study
Synergy between intrathecal omega-conotoxin CVID and dexmedetomidine to attenuate mechanical hypersensitivity in the rat.
The analgesic effects of intrathecal (i.t.) omega-conotoxin CVID, an N-type Ca2+ channel antagonist, and the alpha2-adrenoceptor agonist, dexmedetomidine, were tested alone and in combination following unilateral ligation of L (lumbar) 5/6 spinal nerves in rats. Mechanical allodynia was observed prior to insertion of an i.t. catheter. Effects and interactions of omega-conotoxin CVID (0.01-10 microg/kg) and dexmedetomidine (0.1-10 microg/kg) were tested on allodynic and tail flick (thermal stimulus) responses. ⋯ Both dexmedetomidine and omega-conotoxin CVID completely inhibited allodynia (ED50 0.78+/-0.02 and 0.35+/-0.08 microg/kg, respectively; n=63, 41). Dexmedetomidine and omega-conotoxin CVID combined in dose ratios 0.7 and 1.3 (adjusted for ED50) were synergistic in decreasing mechanical hypersensitivity; interaction index (gamma) 0.39 (confidence interval [CI] 0.33, 0.46) and 0.3 (CI 0.23, 0.38). Despite the necessity for i.t. administration, these data suggest that the synergistic combination confers enhanced potency (lower doses) of both drugs that may avoid clinical toxicity of single drug therapy.