Mol Pain
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Long-term potentiation (LTP) is a key cellular mechanism for pathological pain in the central nervous system. LTP contains at least two different phases: early-phase LTP (E-LTP) and late-phase LTP (L-LTP). Among several major cortical areas, the anterior cingulate cortex (ACC) is a critical brain region for pain perception and its related emotional changes. ⋯ Gabapentin non-selectively decreased basal synaptic transmission. Our results provide strong evidence that the selective AC1 inhibitor NB001 can be used to inhibit pain-related cortical L-LTP without affecting basal synaptic transmission. It also provides basic mechanisms for possible side effects of gabapentin in the central nervous system and its ineffectiveness in some patients with neuropathic pain.
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The current pharmacological treatments for chronic pain are limited. The first analgesic drug approved for clinical use in decades that has a novel molecular target is the synthetic version of a naturally occurring conotoxin. Several conotoxins that target ion channels have progressed to clinical trials for the relief of pain. Vc1.1 and RgIA are analgesic α-conotoxins that target α9-subunit-containing nicotinic acetylcholine receptors (α9-nAChR) as well as GABAB receptor mechanisms. However, the evidence for the involvement of α9-nAChRs in pain is controversial. In the present study, the role of the α9-nAChR in pain was assessed using a battery of behavioural pain tests and pain models in α9-nAChR knockout (KO) mice. ⋯ The α9-nAChR is not involved in acute pain perception or chronic thermal or mechanical allodynia or thermal hyperalgesia but does contribute to the intensity and duration of chronic mechanical hyperalgesia, suggesting that pain-relieving actions of antagonists that target this site may be restricted to high threshold mechanosensation. The α9-nAChR appears to be a valid target for pharmacological compounds that alleviate long-term mechanical hyperalgesia and may be of use as a prophylactic drug to prevent the development of some symptoms of chronic pain.