My friend Matt Ramer and his team at University of British Columbia use our antibodies as markers for sensory neurons. In this important study they use our TRPV1 (Neuromics, Edina, MN, USA; 1:2,000)...Substance P (Neuromics, 1:1,000) and β-III-tubulin (Neuromics; 1:500) to label neuronal profiles in the DRG: Leanne M. Ramer, A. Peter van Stolk, Jessica A. Inskip, Matt S. Ramer and Andrei V. Krassioukov. Plasticity of TRPV1-expressing sensory neurons mediating autonomic dysreflexia following spinal cord injury. DOI=10.3389/fphys.2012.00257.
Highlights: Spinal cord injury (SCI) triggers profound changes in visceral and somatic targets of sensory neurons below the level of injury. Despite this, little is known about the influence of injury to the spinal cord on sensory ganglia. One of the defining characteristics of sensory neurons is the size of their cell body: for example, nociceptors are smaller in size than mechanoreceptors or proprioceptors. In these experiments, we first used a comprehensive immunohistochemical approach to characterize the size distribution of sensory neurons after high- and low-thoracic SCI. Male Wistar rats (300 g) received a spinal cord transection (T3 or T10) or sham-injury. At 30 days post-injury, dorsal root ganglia (DRGs) and spinal cords were harvested and analyzed immunohistochemically. In a wide survey of primary afferents, only those expressing the capsaicin receptor (TRPV1) exhibited somal hypertrophy after T3 SCI. Hypertrophy only occurred caudal to SCI and was pronounced in ganglia far distal to SCI (i.e., in L4-S1 DRGs). Injury-induced hypertrophy was accompanied by a small expansion of central territory in the lumbar spinal dorsal horn and by evidence of TRPV1 upregulation. Importantly, hypertrophy of TRPV1-positive neurons was modest after T10 SCI. Given the specific effects of T3 SCI on TRPV1-positive afferents, we hypothesized that these afferents contribute to autonomic dysreflexia (AD). Rats with T3 SCI received vehicle or capsaicin via intrathecal injection at 2 or 28 days post-SCI; at 30 days, AD was assessed by recording intra-arterial blood pressure during colo-rectal distension (CRD). In both groups of capsaicin-treated animals, the severity of AD was dramatically reduced.
Images: High-thoracic (T3) spinal cord injury had no effect on medium-to-large sized neurons in the L4/L5 DRG expressing heavy neurofilament (NF200). (A) NF200-positive neurons did not undergo SCI-induced hypertrophy, nor did the proportion of neurons expressing NF200 change. (B) Hypertrophy of TRPV1-expressing DRG neurons was not accompanied by increased co-localization of TRPV1 and NF200. Ganglia were harvested 3 months after sham-injury (gray) or complete T3 SCI (black). Arrow: DRG neuron immunopositive for both TRPV1 and NF200. Scale bar = 70 μm.
Conclusion: Previous work has identified numerous mechanisms that might contribute to induction and progression of AD, and the list of putative mechanisms includes injury-induced changes in the vasculature and multiple components of the spinal sensory-sympathetic circuitry caudal to SCI (Krenz and Weaver, 1998; Krassioukov et al., 1999; Krenz et al., 1999; Brock et al., 2006; McLachlan and Brock, 2006). In terms of sensory plasticity, prior findings demonstrate that severity of AD is closely correlated to the extent of intraspinal nociceptor sprouting (Cameron et al., 2006). However, this is the first study to demonstrate AD mediated by a specific subset of afferents that exhibit pronounced somatic, but only slight central, injury-induced plasticity. Given the array of pronounced changes in peripheral targets of sensory neurons after SCI, it is not surprising that they respond to injury. Plasticity occurring outside the CNS may represent a new and more accessible target for limiting sensory-autonomic dysfunction following SCI.
I will keep you posted as more progress is made towards finding therapeutic targets AD.