Pain
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Comparative Study
Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation.
In this study, we recorded activity from afferent fibers innervating the mouse plantar skin, the same region evaluated in pain behavior experiments. We compared responses of afferents from incised and unincised hind paw skin. The plantar skin together with attached medial and lateral plantar nerves was dissected until they could be completely removed intact and placed in an organ bath chamber continuously perfused with oxygenated Kreb's solution with the temperature maintained at 32 degrees C. ⋯ Few fibers were excited by cooling. Heat sensitization of primary afferents was more prominent when activities of unclassified afferents are included. The preparation allows us to study afferent function of the same tissue that is examined for in vivo pain behavior assays in mice.
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Comparative Study
Endogenous kappa-opioid receptor systems inhibit hyperalgesia associated with localized peripheral inflammation.
Peripheral inflammation evokes functional and biochemical changes in the periphery and spinal cord which result in central sensitization and hypersensitivity. Inhibitory control systems from the rostral ventromedial medulla (RVM) are also activated. The present study investigates whether endogenous kappa-opioid receptor (KOPr) systems contribute to these neuroadaptations. ⋯ These data demonstrate a previously unrecognized role of endogenous KOPr systems in inhibiting hyperalgesia during inflammation. Furthermore, they demonstrate that decreased KOPr activity in either the spinal cord or RVM not only enhances mechanical and thermal hyperalgesia of the inflamed limb but also leads to an unmasking of mechanical hyperalgesia at a site remote from inflammation. The differential effects of KOPr antagonism on mechanical versus thermal thresholds for the non-inflamed paw support the notion that distinct neuroanatomical or neurochemical mechanisms modulate the processing of thermal versus mechanical stimuli.
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Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). ⋯ For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.
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Randomized Controlled Trial
Baroreflex sensitivity associated hypoalgesia in healthy states is altered by chronic pain.
While experimental baroreceptor stimulation is known to elicit hypoalgesia in healthy individuals, the impact of spontaneous baroreflex sensitivity (BRS) on acute pain responses is not known. We tested for associations between BRS and pain responses in healthy individuals, whether these associations are altered in chronic low back pain (CLBP), and the role of alpha-2 adrenergic (ADRA2) mechanisms in these effects. Twenty-five healthy controls and 21 CLBP subjects completed three acute pain tasks after receiving placebo or an intravenous ADRA2 antagonist (yohimbine hydrochloride, 0.4 mg/kg) across two sessions in counterbalanced order. ⋯ In contrast, CLBP subjects displayed a nonsignificant positive BRS/pain association under placebo, with yohimbine producing an inverse association similar to controls (significant for MPQ-Sensory). Results suggest presence of spontaneous BRS-related hypoalgesia in healthy individuals that is partially mediated by ADRA2 mechanisms, and that CLBP blunts BRS-related hypoalgesia. As a group, the CLBP subjects do not manifest baroreceptor-induced antinociception.
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The mechanisms of nociception in the low back are poorly understood, partly because systematic recordings from dorsal horn neurons with input from the low back are largely missing. The purpose of this investigation was to (1) identify spinal segments and dorsal horn neurons receiving input from the low back, (2) test the effect of nerve growth factor (NGF) injected into the multifidus muscle (MF) on the neurons' responsiveness, and (3) study the influence of a chronic MF inflammation on the responses. In rats, microelectrode recordings were made in the segments L2, L3, and L5 to find dorsal horn neurons having input from the low back (LB neurons). ⋯ The centers of the neurons' receptive fields (RFs) were consistently located 2-3 segments caudally relative to their recording site. The results show that (1) input convergence from various tissues is common for LB neurons, (2) the input from structures of the low back is processed 2-3 segments cranially relative to the vertebral level of the RFs, and (3) the responsiveness of LB neurons is increased during a pathologic alteration of the MF. The above findings may be relevant for some cases of chronic low back pain in patients.