Prior perineural or neonatal treatment with capsaicin does not alter the development of spinal microgliosis induced by p
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Prior perineural or neonatal treatment with capsaicin does not alter the development of spinal microgliosis induced by peripheral nerve injury Ivett Dorina Szeredi 1 & Gábor Jancsó 1 & Orsolya Oszlács 1 & Péter Sántha 1 Received: 13 March 2020 / Accepted: 14 August 2020 # The Author(s) 2020
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. Keywords Peripheral nerve injury . Microglia . C-fiber afferent . Myelinated afferent . Capsaicin
Introduction Damage to peripheral nerves is often inflicted by common injuries, metabolic disorders, environmental toxins, or therapeutic medications. Functional recovery may be satisfactory after nerve lesions, but the occurrence of neuropathic symptoms is not infrequent. The pathomechanism of nerve injuryinduced pain in man and alterations in nociceptive behavior in experimental animals are complex. Recently, changes in the microenvironment of the neuronal circuitry in the spinal dorsal horn, in particular, an increase in microglial cell density, have gained pivotal importance. Although early studies have demonstrated a substantial increase in microglial density of * Péter Sántha [email protected] 1
Department of Physiology, University of Szeged, Dóm tér 10, Szeged H-6720, Hungary
the spinal cord following peripheral n
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