Articles: hyperalgesia.
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Randomized Controlled Trial Clinical Trial
Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide.
In patients who reported mild postoperative pain, we evoked a nocebo response, a phenomenon equal but opposite to placebo. Patients who gave informed consent to increase their pain for 30 min received a substance known to be non-hyperalgesic (saline solution) and were told that it produced a pain increase. A nocebo effect was observed when saline was administered. ⋯ The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone. These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids. Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety, we suggest that nocebo hyperalgesia may be due to a cholecystokinin-dependent increase of anxiety.
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Randomized Controlled Trial Clinical Trial
Characterisation of capsaicin-induced mechanical hyperalgesia as a marker for altered nociceptive processing in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is characterised by pain and tenderness not only over inflamed or damaged joints, but also over apparently normal tissues. Experimental models suggest that these features results from changes of sensitivity within both peripheral and central neurones, but direct evidence from human disease is lacking. At present, most clinical studies have evaluated overall pain experience rather than activity within components of the nociceptive pathway. ⋯ Peripheral sensory activity over the forearms of rheumatoid patients has previously been shown to be normal and the results suggest the presence of enhanced central mechanisms in this disorder. The correlation between capsaicin-induced hyperalgesia and joint tenderness in the RA patients implies that joint symptoms arise partially as a result of central, and not exclusively peripheral, factors. The study supports the use of capsaicin-based techniques to explore nociceptive mechanisms in clinical disorders characterised by chronic pain.
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Randomized Controlled Trial Clinical Trial
Alfentanil, but not amitriptyline, reduces pain, hyperalgesia, and allodynia from intradermal injection of capsaicin in humans.
Intradermal injection of capsaicin produces brief pain followed by hyperalgesia and allodynia in humans, and the latter effects are mediated by spinal N-methyl-D-aspartate mechanisms. Amitriptyline recently was shown to antagonize N-methyl-D-aspartate receptors, and in this study, the authors sought to determine the effect of amitriptyline alone and with the opioid alfentanil on hyperalgesia and allodynia produced by intradermal injection of capsaicin. ⋯ These data correspond with previous studies in volunteers demonstrating reduction in hyperalgesia and allodynia after intradermal injection of capsaicin by systemically administered opioids, and they suggest that this reduction may be secondary to reduced nociceptive input by acute analgesia. These data do not support the use of acute systemic administration of amitriptyline for acute pain, hyperalgesia, and allodynia, although the roles of chronic treatment and spinal administration are being investigated.
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Chronic inflammatory conditions produce a state of hyperalgesia which is evident from a few hours to days after administration of an inflammatory stimulus. The molecular mechanisms involved in the initiation of hyperalgesia are not well understood and in this study we have investigated the role of prostaglandins in this process in the rat. Unilateral intraplantar injection of Freund's complete adjuvant produces an immediate localized swelling (oedema) with the development of altered pain responses in the ipsilateral paw such as a reduced threshold to noxious stimuli (hyperalgesia) and lowered thresholds such that normally innocuous stimuli produce a pain response (allodynia). ⋯ The marked increase in cyclooxygenase-2 messenger RNA in the lumbar spinal cord following intraplantar Freund's complete adjuvant suggests that the cyclooxygenase enzyme and its product may have a role in the adaptive response that occurs in the lumbar spinal cord during a peripheral inflammatory reaction. Pharmacological analysis reveals that prostaglandins are directly involved in the development of allodynia. However, these studies show that the development of mechanical hyperalgesia does not require the production of prostaglandins indicating that more than one pathway mediates the altered pain responses associated with a peripheral inflammatory lesion.
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1. Peripheral inflammation is characterized by heightened pain sensitivity. This hyperalgesia is the consequence of the release of inflammatory mediators, cytokines and growth factors. ⋯ Intraplantar TNF alpha (100-500 ng) also elevated at 6 but not 48 h the levels of IL-1 beta and NGF in the hindpaw. 7. A single injection of anti-TNF alpha antiserum, 1 h before the CFA, at a dose sufficient to reduce the effects of a 100 ng intraplantar injection of TNF alpha, significantly delayed the onset of the resultant inflammatory hyperalgesia and reduced IL-1 beta but not NGF levels measured at 24 h. 8. The elevation of TNF alpha in inflammation, by virtue of its capacity to induce IL-1 beta and NGF, may contribute to the initiation of inflammatory hyperalgesia.