* Multiple sclerosis (MS) is a neuroinflammatory disease characterised by immune activation, demyelination, and degeneration in the central nervous system (CNS). Chronic pain is a common symptom of MS and current treatment options for pain in MS are ineffective. Pain arises from aberrant excitability of the somatosensory nervous system, typically initiated in the peripheral sensory neurons. To study the underlying immune-mediated pathophysiology of pain in MS, I employed the myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis (EAE) model in mice. Since sensory neurons are crucial for nociceptive transduction, we investigated the effect of this disease on sensory neurons of the dorsal root ganglia (DRG). In Chapter 1, I report that EAE was associated with activation of the complement system and the NLRP3 inflammasome in the DRG. I further observed a transient increase in the number of complement component 5a receptor 1-positive (C5aR1+) immune cells, CD4+ T-cells, and Iba1+ macrophages in the DRG. Moreover, I noted an induction of activating transcription factor 3 (ATF3) at disease onset and chronic disruption of cytoskeletal proteins in the DRG demonstrating neuronal injury in the PNS in response to the disease. Electrophysiological analysis revealed neuronal hyperexcitability at the onset of MOG-EAE signs. In Chapter 2, I investigated the role of NKCC1 and KCC2 in neuropathic pain observed in EAE. Although I observed no change in the levels of NKCC1 transcripts in the DRG throughout the disease course, NKCC1 and KCC2 mRNA levels in the dorsal spinal cord were significantly reduced at disease onset and peak only to recover by the chronic time point. Similarly, Western blot data revealed a significant downregulation of NKCC1 and KCC2 in the dorsal spinal cord at disease onset but an upregulation of NKCC1 protein in the dorsal root ganglia at this time point. Treatment with bumetanide, an NKCC1 inhibitor, had no effect on mechanical hypersensitivity seen in mice with EAE even though it reversed the changes in the levels of NKCC1 and KCC2. In Chapter 3, I investigated whether endoplasmic reticulum (ER) stress in the dorsal root ganglia (DRG) contributes to pain hypersensitivity in EAE and by extension in MS. I observed inflammation and ER stress in post-mortem DRGs from MS patients. My results show that a class of sensory neurons undergo ER stress early in the EAE disease course and relieving ER stress with administration of a chemical chaperone, 4-phenylbutyric acid (4-PBA), can significantly reduce pain hypersensitivity in affected animals. Further in vitro investigations revealed that 4-PBA and AMG44, a selective PERK inhibitor, reduce Ca2+ transients in putative nociceptors. I also identified changes in the functional properties of BK channels in IB4+ neurons. These changes were reversed with 4-PBA and AMG44 application in vitro. Collectively, my results suggest that DRGs in EAE mice and MS patients experience immune activation, inflammation, injury, and ER stress. Using EAE as a proxy to understanding MS pathophysiology, my work also shows that ER stress contributes to pain hypersensitivity by altering Ca2+ dynamics and the functional properties of BK channels, ultimately impacting the electrophysiology of sensory neurons. Hence, novel approaches to treating pain in MS must take into consideration the effect of the disease on the peripheral nervous system.