TRPV1 participates in neuropathic pain after spinal cord injury by mediating the proliferation and activation of CX3CL1-positive glial cells in the spinal dorsal horn

Abstract

Background Patients with spinal cord injury (SCI) often present with different degrees of neuropathic pain (NP). Glia-mediated inflammatory response plays a key role. The transient receptor potential vanilloid subtype 1 (TRPV1), as an ion channel receptor closely related to pain, plays an important role in NP, although its mechanism remains unclear. We explored the role of TRPV1 in NP after SCI and its effect on the proliferation and activation of C-X3-C motif chemokine ligand 1 (CX3CL1)-positive glial cells. Methods The SCI rat model was established using the modified Allen’s spinal cord injury model. After SCI, rats in each group were administered the TRPV1 antagonist SB705498 (10 mg/kg) or 2 mL of vehicle intragastrically for 7 consecutive days. The hindlimb motor function of rats after injury was assessed by the Basso, Beattie, and Bresnahan rating scale; Von Frey fibres and plantar thermal stimulation were used to evaluate the changes in rats’ mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL), respectively; haematoxylin and eosin staining, double immunofluorescent staining, and Western blotting were used to investigate the role of TRPV1 in NP after SCI and its effect on the proliferation and activation of CX3CL1-positive glial cells. Results The chemokine CX3CL1 was mainly expressed in the dorsal horn neurons of the spinal cord and also to a certain extent in microglia, astrocytes, and oligodendrocytes after SCI. The expression of TRPV1 and CX3CL1 in the dorsal horn of the spinal cord in rats was significantly upregulated, and the PWT and PWL of rats were significantly decreased after SCI. The TRPV1 antagonist not only inhibited the activation of TRPV1, but also significantly inhibited the apoptosis of neurons and oligodendrocytes and proliferation and activation of inflammation-related CX3CL1-positive glial cells induced by SCI. Conclusion These results suggest that TRPV1 is involved in the occurrence and development of NP after SCI in rats by mediating the proliferation and activation of CX3CL1-positive glial cells in the dorsal horn of the spinal cord; inhibition of TRPV1 activity attenuates the proliferation and activation of CX3CL1-positive glial cells, thereby reducing symptoms of central sensitisation.