![]() Evidence suggests that hyperactivation of second order sensory neurons in the dorsal horn (DH) of the SC is an important mechanism underlying neuropathic pain. ![]() This can lead to neuropathic pain originating above, below, or at the level of the injury. The complex and vast cascade of events that follows spinal cord (SC) trauma causes pathological alterations at the lesion site but also in regions remote from the injury epicenter and rostral or caudal to the lesion site. Similarly, chronic pain is common among individuals sustaining a SCI and affects quality of life. Chronic pain develops secondary to demyelination, neuroinflammation, and axonal damage in the CNS. Although the disease has been primarily characterized by motor deficits, chronic pain is a disabling symptom experienced by 60% of MS patients. Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system (CNS), whose precise etiology is still unknown. It remains the most challenging type of pain to treat, since conventional therapies are frequently ineffective. Neuropathic pain, a complex and chronic condition, is often associated with various pathologies including multiple sclerosis (MS) and spinal cord injury (SCI). Interleukin-1β is one of the effectors that downregulates PMCA2 by acting directly on neurons. A decrease in PMCA2 in DH neurons is paralleled by increased pain sensitivity, most likely through perturbations in calcium signaling. PMCA2 is a contributor to neuropathic pain mechanisms in the DH. Only IL-1β decreased PMCA2 levels in pure SC neuronal cultures through direct actions. Interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and IL-6 expression were robustly increased in the DH of mice with EAE manifesting pain, whereas these cytokines showed a modest increase or no change in mice with EAE in the absence of pain. In contrast, PMCA2 levels remained unaltered in the DH of mice with EAE that manifested motor deficits but not increased pain. Increased pain in EAE and SCI was paralleled by a significant decrease in PMCA2 levels in the DH. The effectors that decrease PMCA2 expression were identified in SC neuronal cultures. ![]() PMCA2 levels in the lumbar DH were analyzed by Western blotting. Pain was evaluated by the Hargreaves and von Frey filament tests. A severe SC contusion injury was induced at thoracic (T8) level in female C57Bl/6N mice. CFA-inoculated mice were used as controls. MethodsĮAE was induced in female and male C57Bl/6N mice via inoculation with myelin oligodendrocyte glycoprotein fragment 35–55 (MOG 35–55) emulsified in Complete Freund’s Adjuvant (CFA). The present studies investigated the role of PMCA2 in neuropathic pain processing in the DH of wild-type mice affected by experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and following SCI. However, the contribution of PMCA2 to neuropathic pain processing remains undefined. These studies suggested that PMCA2, a calcium extrusion pump expressed in spinal cord neurons, plays a role in pain mechanisms. We previously reported that decreased plasma membrane calcium ATPase 2 (PMCA2) expression in the dorsal horn (DH) of healthy PMCA2 +/− mice is paralleled by increased sensitivity to evoked nociceptive pain. A better understanding of underlying mechanisms could facilitate the discovery of novel targets for therapeutic interventions. I'd appreciate some assistance or advice on getting it to work as intended.Neuropathic pain is often observed in individuals with multiple sclerosis (MS) and spinal cord injury (SCI) and is not adequately alleviated by current pharmacotherapies. I'm new to processing and programming in general and I'm having issues getting the mousePressed function to have the desired effect.
0 Comments
Leave a Reply. |