Pain
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Understanding deep muscle pain is of increasing importance for evaluating clinical pathologic pain states. Previously, a central role of deep muscle tissue in the development of ongoing pain behavior after incision was demonstrated. The underlying mechanisms, however, remain unclear. ⋯ Sensitization of afferents to heat and mechanical stimulation was prominent in group IV afferents after incision; both heat (38.0 vs. 40.5°C in control) and mechanical response threshold (median: 5.0 vs. 22.0 mN in control) were decreased. The finding hat incision increased ongoing activity of muscle afferents is consistent with our previous in vivo studies and supports the idea that deep muscle tissue has a prominent role in the genesis of ongoing pain after incision. The enhanced chemosensitivity of muscle afferents to lactic acid after incision suggests an increased response to an ischemic mediator that may contribute to pain and hyperalgesia caused by surgery in deep tissues.
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Following upper limb peripheral nerve transection and surgical repair (PNIr) patients frequently exhibit sensory and motor deficits, but only some develop chronic neuropathic pain. Thus, the sensorimotor outcome of PNIr may be impacted by individual factors. Therefore, our aims were to determine if patients with chronic neuropathic pain (PNI-P) following PNIr (1) are distinguished from patients without pain (PNI-NP) and healthy controls (HCs) by the psychological factors of pain catastrophizing, neuroticism or extraversion, and (2) exhibit more severe sensorimotor deficits than patients who did not develop chronic pain (PNI-NP). ⋯ Compared to PNI-NP patients, PNI-P patients had higher vibration detection thresholds, performed worse on sensory-motor integration tasks, had greater motor impairment, and showed more impaired nerve conduction. Furthermore, PNI-P patients had reduced cold pain tolerance, elevated pain intensity and unpleasantness during the cold pressor test, and they scored higher on neuroticism and pain-catastrophizing scales. These data demonstrate that chronic neuropathic pain following PNIr is associated with impaired nerve regeneration, profound sensorimotor deficits and a different psychological profile that may be predictive of poor recovery after injury.
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Focused attention typically enhances neural nociceptive responses, reflected electroencephalographically as increased amplitude of pain-evoked event-related potentials (ERPs). Additionally, pain-evoked ERPs are attenuated by hypertension and baroreceptor activity, through as yet unclear mechanisms. There is indirect evidence that these two effects may interact, suggesting that baroreceptor-related modulation of nociception is more than a low-level gating phenomenon. ⋯ Cued stimuli were associated with larger P2 amplitude, but this effect was abolished for stimuli presented during baroreceptor activation. No cardiac timing effect was observed for un-cued stimuli. Taken together, these findings suggest a close integration of cognitive-affective aspects of expectancy and baroreceptor influences on pain, and as such may cast further light on mechanisms underlying mental and physiological contributions to clinical pain.
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The mechanism by which intramuscular injection of BoNTA into the craniofacial muscles decreases migraine headaches is not known. In a blinded study, the effect of BoNTA on the mechanical and chemical responsiveness of individual temporalis muscle nociceptors and muscle neurogenic vasodilation was investigated in female rats. Mechanical threshold was measured for 3h following intramuscular injection of BoNTA or vehicle, and for 10 min after a subsequent injection of the algogen glutamate. ⋯ Additional electrophysiology experiments examined the effect of antagonists for NMDA, CGRP and NK1 receptors on glutamate-induced effects. Glutamate-induced mechanical sensitization was only blocked by the NMDA receptor antagonist, but muscle neurogenic vasodilation was attenuated by NMDA or CGRP receptor antagonists. These data suggest that injection of BoNTA into craniofacial muscles acts to decrease migraine headaches by rapidly decreasing the mechanical sensitivity of temporalis muscle nociceptors through inhibition of glutamate release and by attenuating the provoked release of CGRP from muscle nociceptors.
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This investigation determined whether the activation of the kappa opioid receptor (KOR) in the spinal cord produces estrogen-dependent, sex-specific modulation of acute and inflammation-induced persistent nociception. We demonstrate for the first time that KOR antinociception and gene expression are enhanced by exogenous or endogenous estrogen in the female. The lack of KOR antinociception and KOR gene expression are not altered by the hormonal status (testosterone or estrogen) in males. ⋯ KOR gene expression was enhanced in proestrous and OVX+E groups as compared to any other group. We conclude that selective activation of KOR in the spinal cord produces sex-specific, stimulus- and estrogen-dependent attenuation of acute and inflammatory pain in the rat via estrogen-induced upregulation of the KOR gene expression in the spinal cord. These findings may further implicate estrogen dependence of KOR effects in learning, epilepsy, stress response, addiction etc.