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Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis
I-Ching Wang1,2, Chen-Yen Chung1, Fang Liao1
1Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Rd., Taiwan.
Abstract:
Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain. Elicited pain levels were as high in Asic1a-/-, Asic2-/- and Asic3-/- mice as wild-type mice even though only Asic1a-/- mice showed reduced EAE disease severity, which indicates that pain in EAE was independent of disease severity. We thus adopted an EAE model without pertussis toxin (EAEnp) to restrain activated immunity in the periphery and evaluate the PNS contribution to pain. Both EAE and EAEnp mice showed similar pain behaviors and peripheral neuropathy in nerve fibers and DRG neurons. Moreover, pregabalin significantly reduced neuropathic pain in both EAE and EAEnp mice. Our findings highlight the essential role of the PNS in neuropathic pain in EAE and pave the way for future development of analgesics without side effects in the CNS.
Insights
Neuropathic pain in multiple sclerosis (MS) involves the peripheral nervous system (PNS). This study shows the PNS, not just central nervous system inflammation, drives MS pain, offering new therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Multiple sclerosis (MS) causes debilitating neuropathic pain, often resistant to current treatments.
- Acid-sensing ion channels (ASICs) and peripheral neuropathy are implicated in MS pain, but the peripheral nervous system's (PNS) role remains unclear.
Purpose of the Study:
- To investigate the contribution of ASICs and peripheral neuropathy to MS-induced neuropathic pain.
- To elucidate the role of the peripheral nervous system (PNS) in pain mechanisms.
Main Methods:
- Utilized the experimental autoimmune encephalomyelitis (EAE) rodent model of MS, including a modified model (EAEnp) to focus on peripheral immune responses.
- Assessed pain behaviors, neuropathy in nerve fibers and dorsal root ganglion (DRG) neurons.
- Examined the effects of ASICs gene knockout and pregabalin treatment.
Main Results:
- Pain behaviors and peripheral neuropathy were observed in both EAE and EAEnp models, independent of overall disease severity.
- ASIC-deficient mice showed varied responses, but pain persisted, indicating ASICs are not the sole drivers.
- Pregabalin effectively reduced neuropathic pain in both EAE and EAEnp models.
Conclusions:
- The peripheral nervous system (PNS) plays a critical role in mediating neuropathic pain associated with MS.
- Targeting the PNS may offer novel therapeutic strategies for MS-induced pain.
- Findings suggest potential for developing central nervous system (CNS)-sparing analgesics.
