Role of TRPA1 Channel Expression in Pain Hypersensitivity in EAE Mice
Supervisor / Principle Investigator:
MD Class of 2021
Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system characterized by inflammation, demyelination and neurodegeneration. Along with visual and motor deficits, sensory impairments are common, including neuropathic pain caused by damage or lesion to the somatosensory nervous system. Over 50% of MS patients experience at some stage of their disease course, contributing to disease morbidity. To investigate the molecular mechanisms underlying neuropathic pain in MS, we used a mouse model of experimental autoimmune encephalomyelitis (EAE). Previous research has shown that female mice show decreased pain hypersensitivity when they have access to a running wheel. This decrease in pain has been associated with an increase in interferon-ɣ (IFN-y). To further investigate how running decreases pain hypersensitivity in female mice, we performed quantitative real time PCR on female EAE mice to compare the dorsal root ganglia’s (DRG) cytokine expression. As neuronal hyperexcitability has been linked with pain, we also wanted to assess ion channel expression in EAE mice using qRT-PCR, focusing on TRPA1. We found a trend toward an increase in IFNy in no-pain mice. TRPA1 was also significantly increased in no-pain mice. To further confirm the role of TRPA1 in pain hypersensitivity, we used calcium imaging to assess neuronal hyperexcitability in response to AITC, a TRPA1 agonist. Naïve female mouse DRG cells were cultured in vitro and incubated with splenocyte media from running female EAE mice. Analysis demonstrated that DRG neurons incubated with running splenocyte media showed increased neuronal excitability to AITC, suggesting that TRPA1 channels are upregulated in EAE mice by running. These results suggest that running increases the expression of TRPA1 channels in EAE DRGs, resulting in neuronal hyperexcitability, which is surprisingly associated with decreased pain hypersensitivity. Our results also suggest the IFN-g might play a role in TRPA1 upregulation, but needs further investigation.