Understanding and Treating Neuropathic Pain

• Main Authors: Stemkowski, P.L., Biggs, J.E., Chen, Y., Bukhanova, N., Kumar, N., Smith, P. A.
• Format: Article
• Language: English
• Published: Інститут фізіології ім. О.О. Богомольця НАН України 2013
• Series: Нейрофизиология
• Subjects: Матеріали міжнародного симпозіуму “Молекулярні механізми регуляції синаптичної передачі” (пам’яті В. І. Скока)
• Online Access: http://dspace.nbuv.gov.ua/handle/123456789/148032

Maladaptive neuropathic pain results from injury or disease of the nervous system. It is typically chronic and frequently intractable. Standard analgesics, such as opioids, are of little use, while the gabapentinoids, pregabalin and gabapentin, are not universally effective. In peripherally generated neuropathic pain, an initial inflammatory response releases a variety of mediators, including cytokines and prostaglandins that alter ion channel expression in primary afferent neurons. This initiates ectopic activity in sensory nerves and results in the release of ATP and a second group of mediators from primary afferent terminals. The level of spinal microglial activation is altered such that microglia releases a third set of mediators, notably brain-derived neurotrophic factor (BDNF), in the spinal dorsal horn. Through various mechanisms, BDNF increases excitatory synaptic transmission whilst decreasing inhibitory transmission. The resulting “central sensitization” contributes to the hyperalgesia, causalgia, and allodynia that are associated with neuropathic pain. It is suggested that targeting ion channels in the sensory nerves and excitatory transmission in the dorsal horn may lead to urgently needed new treatments for neuropathic pain. It is also suggested that the effectiveness of gabapentinoids may be increased by combining these agents with the TRPV1 agonist capsaicin.