Abstract
Purpose: Nociplastic pain arises in the body including the orofacial region despite no clear evidence of tissue damage, for which currently available therapeutics do not provide adequate relief. This review extracts pathophysiology and potential therapeutic approaches suggested by research using disease model animals.
Study selection: Fibromyalgia is a typical disease exhibiting nociplastic pain as a main symptom. This review collects and discusses findings in studies using reserpine-induced myalgia （RIM） model animal （rat etc.）, which has been constructed based on the hypothesis that fibromyalgia is triggered by disruption of the antinociceptive regulation by monoamines in the brain.
Results: RIM model animals, simulating patients with fibromyalgia, exhibit nociplastic pain （stimulus-evoked and spontaneous pain symptoms）. It has been shown that pathophysiological changes, including increase of oxidative stress, upregulation of pronociceptive neurotransmitters, and activation of brain immune cells, occur after the chronic reduction of brain monoamines. Potential therapeutic approaches, i.e., 1） functional modification of specific molecules which expression is altered following the monoamine reduction, 2） targeting the molecules which are responsible for other categories of chronic pain （e.g., neuropathic pain）, 3） supplementation of nutrition to correct the disrupted nutritional balance, 4） improvement of physical constitution by natural substances, and 5） nonpharmacological interventions., have been proposed in studies using RIM model animals.
Conclusions: It is expected that translation of findings in RIM model animals to patients would lead to elucidation of pathophysiological mechanisms and development of effective therapeutic approaches to nociplastic pain in the body including the orofacial region.
