Pain
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The conscious perception of somatosensory stimuli is thought to be located in the contralateral cerebral cortex. However, recent human brain imaging investigations in the spinal system report bilateral primary somatosensory cortex (SI) activations during unilateral noxious stimuli and that this ipsilateral spinal representation may be independent of transcallosal connections. In the trigeminal system, there is primate evidence for an ipsilateral somatosensory pathway through the thalamus to the face SI. ⋯ We found that both muscle and cutaneous noxious stimuli, from injections of hypertonic saline into the right masseter or overlying skin, evoked bilateral increases in signal intensity in the region encompassing the ventral posterior thalamus as well as the face region of SI and SII. In contrast, innocuous unilateral brushing of the lower lip evoked a strict contralateral ventroposterior thalamic activation, but bilateral activation of SI and SII. These data indicate that, in contrast to innocuous inputs from the face, noxious information ascends bilaterally to the face SI through the ventroposterior thalamus in humans.
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This study investigated the relation between repetition-induced summation of activity-related pain (RISP) and indicators of functional disability in a sample of 62 individuals who had sustained whiplash injuries. Participants completed measures of pain severity, pain catastrophizing, fear of movement and depression prior to lifting a series of 36 weighted canisters. An index of RISP was computed as the increase in pain reported by participants over successive lifts of the weighted canisters. ⋯ The index of RISP was also significantly correlated with pain catastrophizing and pain duration. The discussion addresses the mechanisms by which physiological and psychological factors might contribute to increases in pain during repeated physical activity. Discussion also addresses whether RISP might represent a risk factor for problematic recovery outcomes following whiplash injury.
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Although the formalin test is a widely used model of persistent pain, the primary afferent fiber types that underlie the cellular and behavioral responses to formalin injection are largely unknown. Here we used a combined genetic and pharmacological approach to investigate the effect of ablating subsets of primary afferent nociceptors on formalin-induced nocifensive behaviors and spinal cord Fos protein expression. ⋯ Remarkably, nocifensive behavior following high-dose (2%) formalin was unchanged in mice lacking either afferent population, or even in mice lacking both populations, which together make up the great majority of C-fiber nociceptors. Thus, at high doses, which are routinely used in the formalin test, formalin-induced "pain" behavior persists in the absence of the vast majority of C-fiber nociceptors, which points to a contribution of a large spectrum of afferents secondary to non-specific formalin-induced tissue and nerve damage.
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Many chronic pain conditions including complex regional pain syndrome are exacerbated by sympathetic activity. In animal models, sympathetic fibers sprout into the dorsal root ganglia (DRG) after peripheral nerve injury, forming abnormal connections with sensory neurons. However, functional studies of sympathetic-sensory connections have been limited largely to in vivo studies. ⋯ In whole DRG isolated 3 days after SNL, microelectrode recordings of sensory neurons showed that repeated stimulation of the dorsal ramus enhanced spontaneous activity in large and medium diameter neurons and reduced rheobase in large neurons. These effects, which were slow and long lasting, were attributed to stimulation of the sympathetic sprouts because: stimulation had no effect in uninjured DRG; and effects could be reduced or eliminated by a "cocktail" of antagonists of norepinephrine and ATP receptors, by pretreatment with the sympathetic release blocker bretylium, or by pre-cutting the grey ramus through which sympathetic fibers coursed to the ligated DRG. The latter treatment, a relatively minimal form of sympathectomy, was also highly effective in reducing mechanical pain ipsilateral to the SNL.
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Through activation of the A1 adenosine receptors (A1Rs) at both the central and peripheral level, adenosine produces antinociception in a wide range of tests. However, the mechanisms involved in the peripheral effect are still not fully understood. Therefore, the mechanisms by which peripheral activation of A1Rs reduces inflammatory hypernociception (a decrease in the nociceptive threshold) were addressed in the present study. ⋯ Direct blockade of PGE(2) inflammatory hypernociception by the activation of A1Rs depends on the nitric oxide/cGMP/Protein Kinase G/KATP signaling pathway because the peripheral antinociceptive effect of CPA was prevented by pretreatment with inhibitors of neuronal nitric oxide synthase (N-propyl-l-arginine), guanylyl cyclase (ODQ), and Protein Kinase G (KT5823) as well as with a KATP blocker (glibenclamide). However, this effect of CPA was not reduced by naloxone, excluding the participation of endogenous opioids. These results suggest that the peripheral activation of A1R plays a role in the regulation of inflammatory hypernociception by a mechanism that involves the NO/cGMP/PKG/KATP intracellular signaling pathway.