Abstract
Tetrodotoxin (TTX) is a potent neurotoxin that blocks voltage-gated sodium channels (VGSCs). VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Alterations in the expression and/or function of some specific TTX-sensitive VGSCs have been implicated in a number of chronic pain conditions. The administration of TTX at doses below those that interfere with the generation and conduction of action potentials in normal (non-injured) nerves has been used in humans and experimental animals under different pain conditions. These data indicate a role for TTX as a potential therapeutic agent for pain. This review focuses on the preclinical and clinical evidence supporting a potential analgesic role for TTX. In addition, the contribution of specific TTX-sensitive VGSCs to pain is reviewed.
Highlights
Pain is a perception and, as a part of the sensory system, has the important protective function of warning us from harm that should be avoided or treated, and prolong survival
Under certain conditions pain loses its protective role and becomes purposeless and highly distressing. This pain condition is related to neuropathic pain, which describes pain occurring with an abnormally functioning somatosensory nervous system to contrast with the normal function seen in nociceptive pain [1]
Marcil et al [107] reported that systemic TTX was most effective in neuropathic pain conditions, based on significant reductions of the mechanical allodynia and thermal hyperalgesia induced by partial sciatic nerve ligation at lower doses than those required to inhibit pain behaviors induced by intraplantar formalin or intraperitoneal acetic acid
Summary
Pain is a perception and, as a part of the sensory system, has the important protective function of warning us from harm that should be avoided or treated, and prolong survival. In this context, behaviors resulting from pain facilitate fundamental biological actions such as the healing of damaged tissues. Under certain conditions pain loses its protective role and becomes purposeless and highly distressing. This pain condition is related to neuropathic pain, which describes pain occurring with an abnormally functioning somatosensory nervous system to contrast with the normal function seen in nociceptive pain [1]. We will examine the roles of TTX-sensitive VGSCs in pain and subsequently, we will highlight the evidences obtained in preclinical animal studies and those studies performed in humans supporting TTX as a potential analgesic compound
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