Pain
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The spared nerve injury (SNI) model involves a lesion of two of the three terminal branches of the sciatic nerve (tibial and common peroneal nerves) leaving the sural nerve intact. The changes in pain-like sensation of the injured animals appear to correlate with a number of symptoms presented in human patients with neuropathic pain syndromes. In order to characterise the SNI model pharmacologically, reflex nociceptive responses to mechanical and cold stimulation were measured after systemic administration of morphine, mexiletine, gabapentin and the glutamate receptor antagonists, MK-801 and NS1209. ⋯ Gabapentin (100 mg/kg, i.p.) significantly alleviated mechanical allodynia for at least 3h, while no significant effects were observed for either mechanical hyperalgesia or cold allodynia. In contrast, the NMDA receptor antagonist MK-801 (0.1 mg/kg, i.p.) and the AMPA receptor antagonist NS1209 (6 mg/kg, i.p.) did not relieve any of the pain-like behaviours of the SNI animals. The present study has shown that a variety of drugs with proven analgesic potency in other models of chronic pain, have differing analgesic profiles in the SNI model of neuropathic pain.
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A noxious cold stimulus can evoke multiple sensations each occurring with a different time course. We have performed psychophysical studies to identify the time course of five sensations evoked by a noxious cold stimulus applied to the hand. Subjects continuously rated either pain, ache, cold, heat or prickle sensations throughout repeated presentations of a noxious cold stimulus (3 degrees C) from a neutral (32 degrees C) baseline. ⋯ Identification of these temporal profiles could provide clues to their underlying mechanisms. The temporal dissociation of these sensations will also enable neuroimaging studies of the cortical mechanisms associated with these sensations. Thus our results constitute a first step toward identifying the distinct modes of neural activity associated with different types of pain sensation.
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Previous evidence indicates that individuals with hypertension and those at increased risk for the disorder exhibit decreased pain perception. To test the hypothesis that attenuation of nociceptive processing in individuals at genetic risk for hypertension is related to differential central modulation of nociceptive transmission, the present study examined descending modulation, alpha-motoneuron excitability, and temporal summation of nociceptive input in young adults with and without a parental history of hypertension. ⋯ Temporal summation was assessed by examining NFR threshold in response to a series of five electrical pulses delivered at 2 Hz. Compared to participants without a parental history of hypertension, offspring of individuals with hypertension exhibited significantly higher NFR thresholds, suggesting that risk for hypertension may be associated with enhanced activation of central pain inhibition pathways.
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Complex regional pain syndrome type I (CRPS I) is a chronic painful disease of one extremity that may develop as a disproportionate consequence of a trauma affecting the limbs without overt nerve injury. It is clinically characterized by sensory, motor and autonomic symptoms including vascular abnormalities. Previously, we have reported that pathophysiological alterations of the ongoing sympathetic activity play a crucial role in vasomotor disturbances (Brain 124 (2001) 587). ⋯ Specificity was 100% at rest and 93% at controlled thermoregulation. We concluded that the degree of unilateral vascular disturbances in CRPS I depends critically on spontaneous sympathetic activity. Taking this into consideration, skin temperature differences in the distal limbs are capable of reliably distinguishing CRPS I from other extremity pain syndromes with high sensitivity and specificity.
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Two unilateral injections of pH 4.0 saline into the gastrocnemius muscle result in a bilateral decrease in mechanical withdrawal threshold after the second injection. This decrease is significant by 4h and lasts through 1 week. The purpose of this study was to characterize the involvement of both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the spinal cord dorsal horn in the development and maintenance of mechanical hyperalgesia from repeated intramuscular injections of acidic saline. 2-amino-5-phosphonovaleric acid (AP5) (2-20 nmol, 10 microl, pH 7) or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo[f]quinoxaline-7-sulfonamide (NBQX) (1-10 nmol, 10 microl, pH 8-9) was administered intrathecally to the lumbar spinal cord to block NMDA and non-NMDA ionotropic glutamate receptors in the dorsal horn, respectively. ⋯ Blockade of non-NMDA glutamate receptors in the spinal cord dorsal horn prior to either the first or second intramuscular injection of pH 4.0 saline had no effect on the development of mechanical hyperalgesia. However, spinal injection of NBQX 1 week after the second intramuscular injection of pH 4.0 saline resulted in an increase in mechanical withdrawal thresholds when compared to vehicle controls. These data suggest that both NMDA and non-NMDA glutamate receptors are involved in the maintenance of chronic, muscle-induced hyperalgesia.