Abstract
Peripheral nerve injury is associated with spinal microgliosis which plays a pivotal role in the development of neuropathic pain behavior. Several agents of primary afferent origin causing the microglial reaction have been identified, but the type(s) of primary afferents that release these mediators are still unclear. In this study, specific labeling of C-fiber spinal afferents by lectin histochemistry and selective chemodenervation by capsaicin were applied to identify the type(s) of primary afferents involved in the microglial response. Comparative quantitative morphometric evaluation of the microglial reaction in central projection territories of intact and injured peripheral nerves in the superficial (laminae I and II) and deep (laminae III and IV) spinal dorsal horn revealed a significant, about three-fold increase in microglial density after transection of the sciatic or the saphenous nerve. Prior perineural treatment of these nerves with capsaicin, resulting in a selective defunctionalization of C-fiber afferent fibers failed to affect spinal microgliosis. Similarly, peripheral nerve injury-induced increase in microglial density was unaffected in rats treated neonatally with capsaicin known to result in a near-total loss of C-fiber dorsal root fibers. Perineural treatment with capsaicin per se did not evoke a significant increase in microglial density. These observations indicate that injury-induced spinal microgliosis may be attributed to phenotypic changes in injured myelinated primary afferent neurons, whereas the contribution of C-fiber primary sensory neurons to this neuroimmune response is negligible. Spinal myelinated primary afferents may play a hitherto unrecognized role in regulation of neuroimmune and perisynaptic microenvironments of the spinal dorsal horn.
Highlights
Damage to peripheral nerves is often inflicted by common injuries, metabolic disorders, environmental toxins, or therapeutic medications
Effect of nerve transection on the distribution and density of spinal microglial cells Staining for isolectin B4 (IB4), a specific neurochemical marker of unmyelinated C-fiber primary sensory neurons, was used to demonstrate the distribution of C-fiber primary afferents in the spinal dorsal horn
Effect of prior perineural application of capsaicin on spinal microgliosis induced by peripheral nerve transection
Summary
Damage to peripheral nerves is often inflicted by common injuries, metabolic disorders, environmental toxins, or therapeutic medications. The pathomechanism of nerve injuryinduced pain in man and alterations in nociceptive behavior in experimental animals are complex. Early studies have demonstrated a substantial increase in microglial density of Available experimental evidence indicates the significance of microglial activation and microglia-derived chemical messengers in the development of neuropathic pain, or painrelated behavior. Several chemokines and tissue mediators, including fractalkine (CX3CL1) (Old and Malcangio 2012), CCL2 (Thacker et al 2009), CCL21 (Biber et al 2011), and ATP (Tsuda et al 2003; Beggs et al 2012), have been implicated in the induction or maintenance of microgliosis, recent findings indicated a pivotal role of peripheral nerve injuryinduced central release of colony stimulating factor 1 in the
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
