Articles: hyperalgesia.
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Effects of chronic constriction injury (CCI) and sham surgery of both sciatic nerves were evaluated for reflex lick/guard (L/G) and operant escape responses to thermal stimulation of rats. Experiment 1 compared L/G and escape responses to 0.3 degrees C, 43 degrees C, and 47 degrees C stimulation during a period of 60 days after CCI. Experiment 2 evaluated escape from 44 degrees C, 47 degrees C, and 10 degrees C for 100 days after CCI. The rats escaped from heat or cold stimulation of the paws in a dark compartment by climbing on a thermally neutral platform in a brightly lit compartment. For reflex testing, a single compartment provided no escape option. There was no significant effect of bilateral CCI on reflex or escape responses to nociceptive heat. However, there were long-term increases in the duration of L/G responding during trials of 0.3 degrees C stimulation and in the duration of escape responding to 10 degrees C. Hyperalgesia for cold was confirmed by a preference test, with a 2-compartment shuttle box with one floor heated (45 degrees C) and the other floor cooled (10 degrees C). Occupancy of the heated compartment was significantly increased by CCI (indicating a relative aversion for cold). ⋯ For preclinical testing of treatments for allodynia/hyperalgesia after nerve injury, it is crucial to use methods of testing that are sensitive to effects on nociception throughout the neuraxis. Operant escape testing satisfies this criterion and is sensitive to bilateral CCI of rats, which avoids asymmetric postural/motor influences of unilateral CCI.
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The relationship between pain and cognitive function is of theoretical and clinical interest, exemplified by observations that attention-demanding activities reduce pain in chronically afflicted patients. Previous studies have concentrated on phasic pain, which bears little correspondence to clinical pain conditions. Indeed, phasic pain is often associated with differential or opposing effects to tonic pain in behavioral, lesion, and pharmacological studies. ⋯ This pain-related activity in medial prefrontal cortex and cerebellum was modulated by the demand level of the cognitive task. Our findings highlight a role for these structures in the integration of motivational and cognitive functions associated with a physiological state of injury. Within the limitations of an experimental model of pain, we suggest that the findings are relevant to understanding both the neurobiology and pathophysiology of chronic pain and its amelioration by cognitive strategies.
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Naunyn Schmiedebergs Arch. Pharmacol. · Aug 2005
Centrally mediated antihyperalgesic and antiallodynic effects of zonisamide following partial nerve injury in the mouse.
Some antiepileptic drugs are used clinically to relieve neuropathic pain. We have evaluated the effects and investigated the possible mechanisms of action of zonisamide, an antiepileptic drug, on thermal hyperalgesia and tactile allodynia in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. Subcutaneously administered zonisamide (10 and 30 mg/kg) produced antihyperalgesic and antiallodynic effects in a dose-dependent manner; these effects were manifested by elevation of the withdrawal threshold in response to a thermal (plantar test) or mechanical (von Frey) stimulus, respectively. ⋯ Moreover, the nitric oxide synthase inhibitor L-NAME, when injected either i.c.v. or i.t., potentiated the analgesic effects of zonisamide. In contrast, neither i.c.v. nor i.t. zonisamide produced antinociceptive effects against acute thermal and mechanical nociception in non-ligated mice. Together, following peripheral nerve injury, it appears that zonisamide produces centrally mediated antihyperalgesic and antiallodynic effects partly via the blockade of nitric oxide synthesis.
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Plasma concentrations of soluble tumor necrosis factor alpha (TNF-alpha) receptor type I (sTNF-RI) were assessed in two complex regional pain syndrome (CRPS) patient groups (n = 30 and n = 16) and healthy controls (n = 25). Patients with CRPS and mechanical hyperalgesia had higher levels of sTNF-RI (1,661.8 +/- 146.8 pg/mL) compared with those with CRPS with identical clinical appearance but without hyperalgesia (1,155.9 +/- 56.3 pg/mL) and controls (1,239.5 +/- 42.9 pg/mL). This study suggests involvement of TNF-alpha in mechanical hyperalgesia of CRPS.
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Neuroscience letters · Jul 2005
Comparative StudyEffects of acute and chronic restraint stress on nitroglycerin-induced hyperalgesia in rats.
Nitric oxide (NO) plays an important role in initiation and maintenance of pain, and NO precursor nitroglycerin is able to activate spinal and brain structures involved in nociception. It is also known that acute and chronic stress induce biochemical changes affecting both pain threshold and behaviour, and that the biological pattern of depression can be mimicked in the laboratory using chronic unavoidable stress paradigms (learned helplessness). We, therefore, evaluated the effects of acute and chronic immobilization stress on pain response to nitroglycerin administration in the rat. ⋯ By contrast, exposition to chronic immobilization stress (7 days) caused a significant increase in pain response (p < 0.05); in this case, hyperalgesia was shown to be further enhanced by nitroglycerin administration (p < 0.05 versus vehicle). These findings support the view that a condition of chronic stress used in the laboratory to reproduce the biological features of depression can enhance hyperalgesia induced by nitroglycerin administration. These observations may be relevant to pain disorders, and particularly to migraine, since nitroglycerin is able to induce spontaneous-like pain attacks in humans, and an unfavourable migraine outcome (transformation into a chronic daily headache) is associated with chronic stress and comorbid depression.