Effects of pelvic nerve axotomy on the neurochemistry of mouse primary afferent neurons and the spinal cord

MCCARTHY, CJ; TOMASELLA, E; SEROOGY, KB; LUNDGREN, KH; MALET, M; HOKFELT, T; VILLAR, M; GEBHART, GF; BRUMOVSKY, PR

Buenos Aires

Congreso; 15th world congress of pain; 2014

International Asociation for the Study of Pain

Peripheral nerve injury results in chronic pain and associated changes in the neurochemistry of primary afferent neurons present in dorsal root ganglia (DRG). Most animal models of peripheral nerve injury are based purely on non-visceral nerves. In contrast, models targeting mixed visceral and non-visceral nerves are less common, even though their injury in humans may be related to some forms of chronic post-surgical pelvic pain. Moreover, information concerning changes in the neurochemistry of DRG neurons after such type of injury, and how they could relate to visceral/viscerosomatic pain, is limited. In the present study we address one of these issues by analyzing potential changes in the expression of a number of neurochemical markers in DRG neurons and the spinal cord of mouse, after pelvic nerve axotomy (PNA). Lumbar 6 (L6) and sacral 1 (S1) spinal nerves, major tributaries of the pelvic nerve, targeting the colorectum, the urinary bladder, reproductive organs and the perineum, were axotomized in BalbC mice. Sham animals were also included. Immunohistochemical expression of several neurochemical markers was analyzed seven days after surgery in L4-S2 dorsal root ganglia (DRG) and spinal cord, including, cyclic AMP-dependent transcription factor 3 (ATF3), calcitonin gene-related peptide (CGRP), transient receptor potential cation channel subfamily V, member 1 (TRPV1), tyrosine hydroxylase (TH), and the vesicular glutamate transporter (VGLUT) types 1 and -2. PNA resulted in strong ATF3-immunoreactive (IR) L6-S1 DRG neuron profiles (NPs) upregulation. This was accompanied by significant downregulations of CGRP-, TRPV1-, TH- and VGLUT2-IR DRG NPs, as compared to their regular expression in uninjured DRGs (contralateral to PNA and sham animals). In contrast, VGLUT1 expression remained unaltered after PNA. Small increases in ATF3-IR NPs were detected in ipsilateral sham L6-S1 DRGs and ipsilateral sham and PNA L4-5 DRGs, suggesting some axonal lesion. However, the latter did not seem to affect the expression of the other neurochemical markers mentioned above. At the lumbosacral spinal cord, PNA also resulted in the upregulation of ATF3 in a number of motor- and parasympathetic preganglionic neurons. In addition, a modest decrease in CGRP- and TRPV1-like-immunoreactive primary afferents terminating in the superficial dorsal horn of the spinal cord was observed ipsilateral to the lesion. Injury of a mixed visceral and non-visceral nerve in mouse leads to considerable neurochemical alterations in DRGs. While more work is necessary, we propose that changes in these and other pain-related molecules may contribute to pain associated to the injury of nerves located in the abdominopelvic cavity. Supported by an Austral University grant and an IASP Early Career Research grant (PRB).