Articles: peripheral-nerve-injuries-physiopathology.
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Neuropathic pain induces allodynia and hyperalgesia. In the spared nerve injury (SNI) model, marked mechanical hyperalgesia is manifested as prolongation of the duration of paw withdrawal after pin stimulation. We have previously reported that spinal ventral root discharges (after-discharges) after cessation of noxious mechanical stimulation applied to the corresponding hindpaw were prolonged in anesthetized spinalized rats. ⋯ Moreover, resiniferatoxin eliminated after-discharges completely. These results show that TRPV1-positive fibers do not participate in the mechanical allodynia caused by sensitization of Aβ-fibers, but contribute to the enhancement of after-discharges and mechanical hyperalgesia following SNI. It is suggested that the mechanisms responsible for generating mechanical allodynia differ from those for prolongation of mechanical hyperalgesia.
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In the clinical setting, skin temperature is both easily evaluated and useful in assessments of sympathetic dysfunction. The present study purposed to observe the serial skin temperature changes of both hindlimbs following several types of sciatic nerve injury (complete transection and ligation model [CTL], crush injury model [CRI], and chronic constriction injury model [CCI]) in Sprague-Dawley rats and, further, to delineate the possible mechanisms through various evaluation methods. The temperature differences between the intact and injured areas (ΔT) on the plantar surface and toes varied among the CTL, CRI, and CCI injury models during the acute stage (7 days post-injury). ⋯ The latency and amplitude of the compound muscle action potential (CMAP) in the involved plantar muscle was not found in the CTL group 4 weeks post-injury, but showed gradual restoration in the CRI and CCI models. Regression analysis revealed that the ΔT in the plantar area and toes were affected only by the CMAP amplitude in the involved plantar muscle; therefore, it can be said that the skin temperature on the injured area after sciatic nerve injury was influenced by the functional status of the involved muscle. Measurement of skin temperature can differentiate mild peripheral nerve injury from moderate-to-severe injuries, although its clinical significance might be limited.
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Neuropathic pain is often a consequence of nerve injury due to surgery, cancer, bone compression, diabetes, or infection. This type of pain can be so severe that even the slightest touch can cause intense pain in the affected area. ⋯ In this review, we summarize the roles of the microglia in the functioning of ATP receptors and of the astrocytes in neuropathic pain. Understanding the key functions of the microglia and astrocytes may lead to the development of new strategies for the management of intractable chronic pain.
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Comparative Study
Geldanamycin accelerated peripheral nerve regeneration in comparison to FK-506 in vivo.
FK-506 accelerates nerve regeneration and improves functional recovery in vivo; its immunosuppressive properties, however, limit its clinical utility. Geldanamycin (GA), a non-immunosuppressive agent, shares a common binding target (heat shock protein 90) with FK-506 and may accelerate nerve regeneration through a similar mechanism. GA has been shown to augment neurite outgrowth in vitro but has not been tested in vivo. ⋯ GA, however, did not match the performance of FK-506 in injury models where Wallerian degeneration (WD) is ongoing in the distal stump. This provides evidence that FK-506 accelerates axonal regeneration through two parallel mechanisms: the first being its well-established effect on neurons; the second is likely a newly described, as-yet poorly defined mechanism that affects WD. Finally, given the decrease in observed toxicity with GA administration, it might be a suitable non-immunosuppressive alternative to FK-506 for accelerating peripheral nerve regeneration in cases of clinical nerve injury.
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Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured)sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut),we investigated (a) neuropathic pain behaviours and (b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). ⋯ We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: (a) increased percentages of C-, Aδ-, and Aβ-nociceptors and cutaneous Aα/β-low-thresholdmechanoreceptors with ongoing/spontaneous firing; (b) spontaneous firing in C-nociceptors that originated peripherally; this was ata faster rate in modified-SNA than SNA; (c) decreased electricalthresholds in A-nociceptors after SNA; (d) hyperpolarised membrane potentials in A-nociceptors and Aα/-low-thresholdmechanoreceptors after SNA, but not C-nociceptors; (e) decreased somatic action potential rise times in C- and A-nociceptors, not Aα/β-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aα/β-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization,and greater evoked pain [corrected].