Pain
-
Cross-sectional research in clinical samples, as well as experimental studies in healthy adults, suggests that the experiences of pain and sleep are bi-directionally connected. However, whether sleep and pain experiences are prospectively linked to one another on a day-to-day basis in the general population has not previously been reported. This study utilizes data from a naturalistic, micro-longitudinal, telephone study using a representative national sample of 971 adults. ⋯ Results suggested that hours of reported sleep on the previous night was a highly significant predictor of the current day's pain frequency (Z=-7.9, p<.0001, in the structural equation model); obtaining either less than 6 or more than 9h of sleep was associated with greater next-day pain. In addition, pain prospectively predicted sleep duration, though the magnitude of the association in this direction was somewhat less strong (Z=-3.1, p=.002, in the structural equation model). Collectively, these findings indicate that night-to-night changes in sleep affect pain report, illuminating the importance of considering sleep when assessing and treating pain.
-
Microneurography was used to record action potentials from afferent C-fibers in cutaneous fascicles of the peroneal nerve in healthy volunteers. Afferent fibers were classified according to their mechanical responsiveness to von Frey stimulation (75g) into mechano-responsive and mechano-insensitive nociceptors. Various concentrations of Endothelin1 (ET1) and Histamine were injected into the receptive fields of C-fibers. ⋯ No wheal was observed after injection of ET1. Both itching and pain were decreased after H1 blocker treatment. In summary: (1) In humans ET1 activates mechanosensitive, but not mechano-insensitive, nociceptors. (2) Histamine released from mast cells is not responsible for all effects of ET1 on C-nociceptors. (3) ET1 could have a differential role in pain compared to other chemical algogens which activate additionally or even predominantly mechano-insensitive fibers.
-
Comparative Study
C-fiber spontaneous discharge evoked by chronic inflammation is suppressed by a long-term infusion of lidocaine yielding nanogram per milliliter plasma levels.
Nociceptors innervating inflamed tissue acquire an abnormal spontaneous discharge that is believed to be at least part of the reason for the persistent spontaneous pain, allodynia, and hyperalgesia that accompany inflammation. Recent studies suggest that patients with chronic inflammatory pain may obtain an analgesic effect with transdermal application of lidocaine that yields very low plasma levels (130-225 ng/ml). The aim of this study was to investigate whether a 7-day exposure to such low plasma levels of lidocaine had an effect on inflammation-evoked spontaneous discharge in the rat. ⋯ Lidocaine infusion had no effect on the incidence of spontaneous discharge in muscle or cutaneous A-fibers. Lidocaine infusion reduced mechano-hyperalgesia but had no effect on mechano-allodynia or heat-hyperalgesia. We conclude that the analgesic effects seen clinically with transdermal lidocaine administration yielding low plasma levels may be due to a systemic drug action on spontaneously active C-fibers.
-
Neuropathic pain consequent to peripheral injury is associated with local inflammation and overexpression of nitric oxide synthases (NOS) and inflammatory cytokines in locally recruited macrophages, Schwann and glial cells. We investigated the time course and localization of nitric oxide synthases (NOS) and cytokines in the central (spinal cord and thalamus) and peripheral nervous system (nerve and dorsal root ganglia), in a mouse model of mononeuropathy induced by sciatic nerve chronic constriction injury. ATP is recognized as an endogenous pain mediator. ⋯ PPADS (25mg/kg) completely reversed nociceptive hypersensitivity and simultaneously reduced the increased NO/NOS system and IL-1beta in both peripheral (injured sciatic nerve and L4-L6 ipsilateral dorsal root ganglia) and central steps of nervous system (L4-L6 spinal cord and thalamus) involved in pain signalling. IL-6 was overexpressed only in the peripheral nervous system and PPADS prolonged administration reduced it in sciatic nerve. In conclusion, we hypothesize that NO/NOS and IL-1beta have a pronociceptive role in this neuropathy model, and that purinergic antagonism reduces pain hypersensitivity by inhibiting their overactivity.
-
Comparative Study
Complement activation in the peripheral nervous system following the spinal nerve ligation model of neuropathic pain.
Neuroinflammatory and neuroimmune mechanisms, as exemplified by infiltrating immune cells and activation of resident endothelial/glial cells, respectively, are known to be involved in the establishment and maintenance of chronic pain. An immune system pathway that may be involved in the activation of both immune and glial cells is complement. The complement pathway is made up of a large number of distinct plasma proteins which react with one another to opsonize pathogens and induce a series of inflammatory responses to help fight infection. ⋯ To test the hypothesis that complement plays a role in neuropathic pain, SNL rats were treated with cobra venom factor (CVF) to deplete plasma of complement component C3. Pain behavior was significantly attenuated in SNL rats treated with CVF as was complement activity at the ipsilateral dorsal root ganglia. Our results suggest the complement pathway might be a novel target for the development of neuropathic pain therapeutics.