Articles: hyperalgesia.
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Spinal cord transplants of embryonic cortical GABAergic progenitor cells derived from the medial ganglionic eminence (MGE) can reverse mechanical hypersensitivity in the mouse models of peripheral nerve injury- and paclitaxel-induced neuropathic pain. Here, we used electrophysiology, immunohistochemistry, and electron microscopy to examine the extent to which MGE cells integrate into host circuitry and recapitulate endogenous inhibitory circuits. Whether the transplants were performed before or after nerve injury, the MGE cells developed into mature neurons and exhibited firing patterns characteristic of subpopulations of cortical and spinal cord inhibitory interneurons. ⋯ Unexpectedly, MGE cells transplanted before injury prevented the development of mechanical hypersensitivity. Together, our findings provide direct confirmation of an extensive, functional synaptic integration of MGE cells into host spinal cord circuits. This integration underlies normalization of the dorsal horn inhibitory tone after injury and may be responsible for the prophylactic effect of preinjury transplants.
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The Journal of physiology · Nov 2016
Secondary hyperalgesia is mediated by heat-insensitive A-fibre nociceptors.
It is believed that secondary hyperalgesia (the increased sensitivity to mechanical nociceptive stimuli that develops after cutaneous tissue injury in the surrounding uninjured skin) is mediated by a subclass of nociceptors: the slowly adapting A-fibre mechano-heat nociceptors (AMH-type I). Here we tested this hypothesis. By using intense long-lasting heat stimuli, which are known to activate these slowly adapting AMH-type I nociceptors, we show that the perceived intensity elicited by these stimuli is not increased in the area of secondary hyperalgesia. Moreover, we show that during an A-fibre nerve conduction block the perception elicited by the long-lasting heat stimuli is significantly reduced in a time window that matches the response profile of the AMH-type I nociceptors. AMH-type I nociceptors contribute to the perception of sustained heat, but they do not mediate secondary hyperalgesia. Therefore, we propose that secondary hyperalgesia is mediated by high threshold mechanoreceptors. ⋯ Secondary hyperalgesia refers to the increase in sensitivity to mechanical nociceptive stimuli delivered outside the area of tissue injury. Previous studies have suggested that secondary hyperalgesia is mediated by a specific class of myelinated nociceptors: slowly adapting A-fibre mechano- and heat-sensitive (AMH) type I nociceptors. Here, we tested this hypothesis by examining whether long-lasting heat stimuli, which are known to activate AMH-type I nociceptors, elicit enhanced responses when delivered to the area of secondary hyperalgesia induced by high frequency electrical stimulation of the skin (HFS). Before and 20 min after HFS, sustained 30 s radiant heat stimuli were delivered to the area of increased mechanical pinprick sensitivity while participants continuously rated intensity of perception using an online visual analog scale (0-100 mm). After HFS, no significant enhancement of heat perception was observed in the area of increased pinprick sensitivity. To establish that myelinated nociceptors actually contribute to the perception of sustained heat, we conducted a second experiment in which sustained heat stimuli were presented before and during an A-fibre nerve conduction block, achieved by applying a rubber band with weights which compresses the superficial radial nerve against the radius. During the block, heat perception was significantly reduced 17-33 s after the onset of the heat stimulus (before: mean = 53 mm, during: mean = 31 mm; P = 0.03), matching the response profile of AMH-type I nociceptors. These results support the notion that AMH-type I nociceptors contribute to the perception of sustained heat, but also show that these afferents do not mediate secondary hyperalgesia.
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Neuroscience letters · Nov 2016
Spinal mitochondrial-derived ROS contributes to remifentanil-induced postoperative hyperalgesia via modulating NMDA receptor in rats.
Activation of N-methyl-d-aspartate (NMDA) receptor by reactive oxygen species (ROS) in the spinal cord plays an important role in the development of hyperalgesia in several neuropathic pain models. The study examined the involvement of ROS-NMDA signaling pathway in remifentanil-induced postoperative hyperalgesia. ⋯ These findings indicated that ROS-dependent activation of NMDA receptor in the spinal cord might be a potential mechanism underlying remifentanil-induced postoperative hyperalgesia.
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Experimental neurology · Nov 2016
Acute spinal cord injury (SCI) transforms how GABA affects nociceptive sensitization.
Noxious input can sensitize pain (nociceptive) circuits within the spinal cord, inducing a lasting increase in spinal cord neural excitability (central sensitization) that is thought to contribute to chronic pain. The development of spinally-mediated central sensitization is regulated by descending fibers and GABAergic interneurons. The current study provides evidence that spinal cord injury (SCI) transforms how GABA affects nociceptive transmission within the spinal cord, recapitulating an earlier developmental state wherein GABA has an excitatory effect. ⋯ DIOA) in intact rats mimicked the effect of SCI. Conversely, a pharmacological treatment (bumetanide) that should increase intracellular Cl- levels blocked the effect of SCI. The results suggest that GABAergic neurons drive, rather than inhibit, the development of nociceptive sensitization after spinal injury.
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Int J Psychophysiol · Nov 2016
Randomized Controlled TrialExpectation of nocebo hyperalgesia affects EEG alpha-activity.
Changes in EEG activity have been related to clinical and experimental pain. Expectation of a negative outcome can lead to pain enhancement (nocebo hyperalgesia) and can alter the response to therapeutic interventions. The present study characterizes EEG alteration related to pain facilitation by nocebo. ⋯ Five-minute EEG was recorded under: resting state, tonic innocuous heat and tonic noxious heat before and after the application of a sham inert cream to the non-dominant volar forearm combined with cognitive manipulation. The intensity and unpleasantness of heat-induced pain increased after cognitive manipulation in the nocebo group compared to control and was associated with enhanced low alpha (8-10Hz) activity. However, changes in alpha activity were predicted by catastrophizing but not by pain intensity or unpleasantness, which suggest that low alpha power might reflect brain activity related to negative cognitive-affective responses to pain.