Abstract
The term “nociplastic pain,” a recently proposed novel mechanistic descriptor of chronic pain, is defined as pain that arises from altered nociception without nociceptor activation and nerve injury1）. Diseases with the nociplastic pain include fibromyalgia, complex regional pain syndrome, irritable bowel syndrome, chronic primary temporomandibular disorder pains, and burning mouth syndrome. Since there is no established pharmacotherapy for these diseases, developing drugs that effectively mitigate aberrant nociception in conditions characterized by nociplastic pain becomes an urgent issue. However, the limited availability of preclinical murine models hampers the evaluation of nociplastic pain without nociceptor activation or injury2）.
In this context, we present our recently developed model for nociplastic pain. Through a single subcutaneous injection of formalin into the upper lip, sustained sensitization lasting over 13 days at the bilateral hind paws occurs despite the absence of injury or neuropathy in rats and mice3）. Using this nociplastic pain model, we demonstrated that repeated daily injections of pregabalin （PGB）, a drug conventionally employed to treat neuropathic pain, transiently attenuated sensitization in bilateral hind paws for the first 6 days following the initial inflammation4）. By the 10th day of formalin injection, hindlimb sensitization was significantly reduced, even without PGB, implying its action site within the brain’s pain network4）. This review encompasses the presentation of our obtained results, along with a discussion of potential future strategies for nociplastic pain treatment.
