Pain
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This electrophysiological study examined the effects of NSAID administration on synaptically-elicited responses of rat single spinal dorsal horn neurons to natural stimulation of peripheral receptive fields. Nociceptive responses consisted of a fast initial discharge during the stimulus followed by a slowly-decaying afterdischarge. The cyclooxygenase inhibitor, indomethacin (2.0-8.0 mg/kg, i.v.), was without effect on the on-going rate of discharge but dose-dependently inhibited synaptically-elicited responses to noxious cutaneous mechanical stimulation (fast initial discharge: n = 3/3 with 2 mg/kg, 5/8 with 4 mg/kg, 5/6 with 8 mg/kg; slowly-decaying afterdischarge: n = 3/3 with 2 mg/kg, 6/8 with 4 mg/kg, 6/6 with 8 mg/kg) and thermal (fast initial discharge: n = 7/9 with 8 mg/kg; slowly-decaying afterdischarge: n = 3/4 with 4 mg/kg, n = 7/9 with 8 mg/kg). ⋯ The data are interpreted to suggest that sensory inputs are more involved than input-independent excitation of dorsal horn neurons in leading to de novo synthesis of eicosanoids and that the time course of this synthesis brings the levels to a point where COX inhibition can have an observable effect during prolonged excitation. Although the data suggest that COX inhibition differentially inhibits nociceptive versus non-nociceptive mechanisms at the cellular level, irrespective of the modality of the stimulus, this is the first direct demonstration that prolonged activation of synaptic mechanisms are preferentially inhibited. According to this it would be predictable that NSAIDs would be more effective on nociceptive types of pain characterized by time or prolonged inputs of primary afferents.
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Cannabinoid receptor (CB1) agonists strongly inhibit behavioral responses to acute noxious stimuli, but their effects on behavioral responses in persistent pain states are less clear. Here, we examined the effects of intrathecal (i.t.) administration of a CB1 agonist, WIN55,212-2, on mechanical allodynia (decreased withdrawal threshold) produced by injections of complete Freund's adjuvant (CFA) in the plantar surface of the rat hindpaw. We measured mechanical thresholds with calibrated von Frey filaments before and after CFA and used Fos expression as a marker of the activity of spinal cord neurons during inflammation and in response to a CB1 antagonist. ⋯ In normal animals, the increase was primarily in laminae V-VI and in the ventral horn; in animals with persistent inflammation SR141716A increased the number of Fos neurons in laminae I-II and V-VI. These results demonstrate that WIN55212-2 reverses inflammation-induced allodynia at doses that do not produce analgesia and that SR141716A differentially affects the pattern of Fos expression in the spinal cord, depending on the presence or absence of inflammation. Taken together, these results suggest that the CB1 receptor system is tonically active in the spinal cord under normal conditions and that its activity is increased in response to injury.
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Clinical Trial Controlled Clinical Trial
Dissociation of sensory and affective dimensions of pain using hypnotic modulation.
Understanding the complex nature of pain perception requires the ability to separately analyze its psychological dimensions and their interaction, and relate them to specific variables and responses. The present study, therefore, attempted to selectively modulate the sensory and affective dimensions of pain, using a cognitive intervention, and to assess the possible relationship between these psychological dimensions of pain and changes in physiological responses to the noxious stimuli. In three experiments, normal subjects trained in hypnosis rated pain intensity and pain unpleasantness produced by a tonic heat-pain stimulus (1-min immersion of the hand in 45.0-47.5 degrees C water). ⋯ Wade JB, Dougherty LM, Archer CR, Price DD. Assessing the stages of pain processing: a multivariate analytical approach. Pain 1996;68:157-167) which provides a conceptual framework necessary to study the cerebral representation of pain perception.
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Clinical Trial
C- and A delta-fiber components of heat-evoked cerebral potentials in healthy human subjects.
Feedback-controlled laser heat was used to stimulate the hairy skin of the hand dorsum and forearm, and heat-evoked cerebral potentials were recorded at midline (Fz, Cz, Pz) and temporal (T3, T4) scalp positions. Based on data from primary afferent electrophysiology a stimulus level (40 degrees C) was chosen, which is above C-fiber heat threshold, but clearly below A delta-nociceptor heat threshold in order to excite selectively C-fibers without concomitant excitation of A delta-fibers. Feedback-controlled stepped heat stimuli to 40 degrees C elicited ultralate laser evoked potentials (LEPs) at the vertex in a high proportion of experiments (90%). ⋯ The LEP waveform to strong heat stimuli also contained an ultralate component reminiscent of an ultralate LEP following the late LEP. Ultralate and late LEP had identical scalp topography. In conclusion, the method of temperature-controlled laser heat stimuli allows the selective and reliable examination of A delta- and C-fiber-mediated afferent pathways and the related cortical processing without the complication of dissociating A-fiber nerve blocks.
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We have previously shown that Fos-like immunoreactivity (Fos-LI) is evoked in the brainstem of ferrets following stimulation of pulpal A delta and C fibers originating from the maxillary canine. This study evaluated the effects of the mu-opioid receptor agonist fentanyl on Fos expression evoked by noxious thermal stimulation of the right maxillary and mandibular canines in pentobarbital/chloral hydrate anesthetized adult male ferrets. Pulpal heating evoked Fos expression in two distinct regions of the spinal trigeminal nuclear complex: the transitional region between subnucleus interpolaris and caudalis (Vi/Vc) and within the subnucleus caudalis (Vc). ⋯ The administration of naloxone without heat stimulation failed to evoke Fos expression in Vi/ Vc and Vc. These findings suggest that the activation of trigeminal Vi/Vc and Vc neurons by noxious dental heat stimulation is controlled by a naloxone sensitive endogenous opioid system as indicated by Fos expression. Collectively, these results suggest that neuronal populations in Vi/Vc and Vc regions may contribute to pain responses to noxious dental stimulation and these responses can be modulated by both endogenous and exogenous opioids.