Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis.
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.
Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Rd., Taiwan.|Department of Life Science, National Taiwan University, Taiwan.
I-Ching
IC
Wang
Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Rd., Taiwan.
Chen-Yen
CY
Chung
Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Rd., Taiwan.
Fang
F
Liao
Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Rd., Taiwan.|Department of Life Science, National Taiwan University, Taiwan.
Chih-Cheng
CC
Chen
Institute of Biomedical Sciences, Academia Sinica, 128, Sec. 2, Academia Rd., Taiwan.
Cheng-Han
CH
Lee
D062565:Acid Sensing Ion Channels / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003711:Demyelinating Diseases / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066128:Gray Matter / Q000187:drug effects / Q000473:pathology; D006930:Hyperalgesia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism; D009437:Neuralgia / Q000150:complications* / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism; D017933:Peripheral Nervous System / Q000293:injuries* / Q000473:pathology* / Q000503:physiopathology; D000069583:Pregabalin / Q000494:pharmacology / Q000627:therapeutic use; D011984:Sensory Receptor Cells / Q000473:pathology*
D062565:Acid Sensing Ion Channels; D000700:Analgesics; D010455:Peptides; D000069583:Pregabalin