Pain
-
Pain relief by touch has been studied for decades in pain neuroscience. Human perceptual studies revealed analgesic effects of segmental tactile stimulation, as compared to extrasegmental touch. However, the spatial organisation of touch-pain interactions within a single human dermatome has not been investigated yet. ⋯ Touch also produced a bias to judge laser stimuli as less painful. This bias decreased linearly when the distance between the laser and tactile stimuli increased. Thus, our study provides evidence for a spatial organisation of intrasegmental touch-pain interactions.
-
The analgesic effect of heterotopic noxious counter-stimulation (HNCS; "pain inhibits pain") has been shown to decrease in older persons, while some neuropsychological studies have suggested a reduction in cognitive inhibition with normal aging. Taken together, these findings may reflect a generalized reduction in inhibitory processes. The present study assessed whether the decline in the efficacy of pain inhibition processes is associated with decreased cognitive inhibition in older persons. ⋯ Increased cognitive interference (ie, larger Stroop effect) correlated with smaller inhibition of the RIII reflex by HNCS across groups (r=-.34, P=0.025). This association was independent from the age-related slowing observed in control reading and naming tasks. These results suggest a generalized age-related reduction in inhibitory processes affecting both executive functions and cerebrospinal processes involved in the regulation of pain-related responses induced by competing nociceptive threats.
-
The pathophysiology of the complex regional pain syndrome involves enhanced neurogenic inflammation mediated by neuropeptides. Neutral endopeptidase (neprilysin, NEP) is a key enzyme in neuropeptide catabolism. Our previous work revealed that NEP knock out (ko) mice develop more severe hypersensitivity to thermal and mechanical stimuli after chronic constriction injury (CCI) of the sciatic nerve than wild-type (wt) mice. ⋯ Gene expression of the ET-1 receptors ETAR and ETBR was not different between genotypes and was not altered after CCI, but was increased after additional MP treatment. The ETBR agonist IRL-1620 was analgesic in NEP ko mice after CCI, and the ETBR antagonist BQ-788 showed a trend to reduce the analgesic effect of MP. The results provide evidence that MP reduces CCI-induced hyperalgesia in NEP ko mice, and that this may be related to ET-1 via analgesic actions of ETBR.
-
Prostacyclin is an important mediator of peripheral pain sensation. Here, we investigated its potential participation in mediating neuropathic pain and found that prostacyclin receptor (IP) knockout mice exhibited markedly decreased pain behavior. Application of an IP antagonist to the injury site or selective IP deficiency in myeloid cells mimicked the antinociceptive effect observed in IP knockout mice. ⋯ Fittingly, the IL1-receptor antagonist anakinra (IL-1ra) decreased neuropathic pain behavior in wild-type mice but not in IP knockout mice. Finally, continuous, but not single administration, of the cyclooxygenase inhibitor meloxicam early after nerve injury decreased pain behavior and the number of resident macrophages. Thus, early synthesis of prostacyclin at the site of injury causes accumulation of IL1β-expressing macrophages as a key step in neuropathic pain after traumatic injury.
-
After peripheral nerve injury, nociceptive afferents acquire an abnormal excitability to adrenergic agents, possibly due to an enhanced expression of α1-adrenoceptors (α1-ARs) on these nerve fibres. To investigate this in the present study, changes in α1-AR expression on nerve fibres in the skin and sciatic nerve trunk were assessed using immunohistochemistry in an animal model of neuropathic pain involving partial ligation of the sciatic nerve. In addition, α1-AR expression on nerve fibres was examined in painful and unaffected skin of patients who developed complex regional pain syndrome (CRPS) after a peripheral nerve injury (CRPS type II). ⋯ In each patient examined, α1-AR expression was greater on nerve fibres in skin affected by CRPS than in unaffected skin from the same patient or from pain-free controls. Together, these findings provide compelling evidence for an upregulation of α1-ARs on cutaneous nociceptive afferents after peripheral nerve injury. Activation of these receptors by circulating or locally secreted catecholamines might contribute to chronic pain in CRPS type II.