Nociplastic mechanisms in temporomandibular disorders: Separating nociception from pain

Project Summary: Quantitative sensory testing (QST) is widely used to make inferences about pain processing mechanisms, including how processing is disrupted in chronic pain. However, it is usually not possible to separate nociceptive from pain sensitivity in these studies. For QST, this means that true, unbiased nociceptive

sensitivity cannot be measured using psychophysical techniques that have provided insight into other sensory modalities. To overcome these challenges, we developed a method to selectively stimulate nociceptors by locating fairly large (>2.56 cm2) naturally occurring areas of skin that are completely devoid of innocuous warm

fibers. By applying noxious heat to these warmth-insensitive regions, we are able to obtain unbiased measures of nociceptive sensitivity and compare those with measures of pain sensitivity using the same stimuli (noxious heat). Nociplastic pain, which is a different mechanistic category from nociceptive and neuropathic, is present in

many chronic pain conditions, including temporomandibular disorders (TMD). However, some patients likely have more nociplastic mechanisms than others. To extend our knowledge of the mechanisms contributing to nociplastic pain, this project will enroll both pain-free individuals and those with TMD and employ 1) standardized

QST procedures for assessment of nociplastic pain, multimodal sensory hypersensitivity, and comparison with other chronic pain conditions like neuropathic pain and fibromyalgia, 2) a novel nociceptive-specific heating (NoSH) protocol to measure the sensitivity of nociceptors in relation to the perception of pain, and 3) a variety of

endogenous pain-modulatory processes that might contribute to nociceptive and/or pain hypersensitivity in patients with nociplastic pain. We hypothesize that a subset of TMD patients will display highly probable nociplastic pain according to the clinical grading criteria. Based on preliminary data, we hypothesize that pain

hypersensitivity is related to suprathreshold mechanisms that modulate nociceptive signals differently in nociplastic pain. Success in this project could also lead to development of a new clinical biomarker for assessing nociception and pain in isolation.