Neuroplasticity of ascending and descending pathways after somatosensory system injury: reviewing knowledge to identify neuropathic pain therapeutic targets

STUDY DESIGN: This is a narrative review of the literature. OBJECTIVES: This review aims to be useful in identifying therapeutic targets. It focuses on the molecular and biochemical neuroplasticity changes that occur in the somatosensory system, including ascending and descending pathways, during the development of neuropathic pain. Furthermore, it highlights the latest experimental strategies, based on the changes reported in the damaged nociceptive neurons during neuropathic pain states. SETTING: This study was conducted in Girona, Catalonia, Spain. METHODS: A MEDLINE search was performed using the following terms: descending pain pathways; ascending pain pathways; central sensitization; molecular pain; and neuropathic pain pharmacological treatment. RESULTS AND CONCLUSION: Neuropathic pain triggered by traumatic lesions leads to sensitization and hyperexcitability of nociceptors and projection neurons of the dorsal horn, a strengthening in the descendent excitatory pathway and an inhibition of the descending inhibitory pathway of pain. These functional events are associated with molecular plastic changes such as overexpression of voltage-gated ion channels, algogen-sensitive receptors and synthesis of several neurotransmitters. Molecular studies on the plastic changes in the nociceptive somatosensory system enable the development of new pharmacological treatments against neuropathic pain, with higher specificity and effectiveness tha