Pathophysiology of Active and Latent Myofascial Trigger Points - PROJECT SUMMARY Pain deriving from a range of health concerns including headache, low back pain, osteoarthritis, carpal tunnel syndrome, as well as post-surgical and cancer pain have been linked to myofascial trigger points (TrPs). The TrP is a tender nodule along a taut band of muscle. Two states of the TrP are known to exist: active and latent. In the active state, the TrP is spontaneously painful and elicits pain referral mimicking the clinical complaint. The latent TrP is not spontaneously painful and any referred pain it elicits upon palpation is not related to a clinical pain complaint; the latent TrP is thought to be an intermediary state between healthy and an active TrP. Evidence from ultrasound indicates latent TrPs exhibit reduced blood flow, which is further reduced in active TrPs, suggestive of metabolic disruption and cellular stress. In line with that observation, hypothesized TrP models predict reduced glucose and elevated lactate in TrPs, however a pilot massage intervention trial that reduced active TrP pain found no change in glucose and an increase in lactate. The discrepancy between the TrP model and empirical evidence argues that cellular metabolism within a TrP may behave differently than the well-accepted model predicts. Lactate has also been linked to nociceptor sensitization, which could explain differences in local or referred pain experience. Furthermore, the differences in blood flow between latent and active TrPs could result in metabolic differences that may be informative as to the formation, progression, and perpetuation of TrPs. The present study will use a targeted and non-targeted metabolomics approach to understand the metabolic environment within both types of trigger points and healthy muscle. Latent TrPs from healthy individuals and active TrPs from individuals with tension-type headache will be investigated. The targeted approach will focus on glucose and lactate to determine whether carbohydrate energy balance is different within healthy muscle and trigger point sites. The non-targeted approach will screen for thousands of metabolic biomarkers within healthy muscle and the TrPs to identify relative differences in metabolites that could identify which metabolites lead to development of a latent TrP, progression to an active TrP, or perpetuation of the active TrP. The experiments described in this proposal will provide insight into the internal environment of TrPs. Should this exploratory study reveal disruption to carbohydrate energy balance or identify differences in biomarkers within latent or active TrPs a mechanism for the formation or progression of the TrP will become clear. This information could be used to optimize intervention techniques that will reverse or prevent muscle-derived pain. This proposed study will address the key goal to “Develop and validate biomarkers for chronic pain or other key symptoms to be used in studies of mind and body approaches” from the Funding Opportunity Announcement PA-18-322.