Pain
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Microelectrode recordings of impulse activity in nociceptive C fibres were performed in cutaneous fascicles of the peroneal nerve at the knee level in healthy human subjects. Mechano-heat responsive C units (CMH), mechano-insensitive but heat-responsive (CH) as well as mechano-insensitive and heat-insensitive C units (CM(i)H(i)) were identified. A subgroup of the mechano-insensitive units was readily activated by histamine. ⋯ In conclusion, we have shown that ATP injections at high concentrations activate C-nociceptors in healthy human skin, without preference for mechano-responsive or mechano-insensitive units. ATP did not sensitise human C fibres for mechanical or heat stimuli. We discuss how various mechanisms might contribute to the observed responses to ATP.
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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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Recent studies indicate that sustained opioid administration produces increased expression of spinal dynorphin, which promotes enhanced sensitivity to non-noxious and noxious stimuli. Such increased "pain" may manifest behaviorally as a decrease in spinal antinociceptive potency. Here, the possibility of similar mechanisms in the antinociception of spinal cannabinoids was explored. ⋯ Daily MK-801 pretreatments, prior to WIN 55,212-2 injection, also produced a significant block of antinociceptive tolerance. These data suggest that like opioids, repeated spinal administration of a cannabinoid CB1 agonist elicits abnormal pain, which results in increased expression of spinal dynorphin. Manipulations that block cannabinoid-induced pain also block the behavioral manifestation of cannabinoid tolerance.
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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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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.