For the administrative supplement, only the following research areas will be considered:

1) Basic/Mechanistic, Translational, or Clinical Research on Pain Related to Sickle Cell Disease. Sickle cell disease (SCD) predominantly affects individuals of African descent and those who self-identify as Black. The most common complication of SCD is pain, including severe acute pain episodes and chronic persistent pain, which can be devastating and often requires opioid treatment. Our understanding of the biological cause(s) of pain in patients with sickle cell disease is very inadequate as the extant literature directly addressing the biological mechanisms underlying major clinical features of this painful condition is extremely limited. Furthermore, significant gaps remain in translation of research from bench to beside. Exploratory studies to address these gaps and advance our knowledge on fundamental processes in SCD pain and potential treatments with a variety of therapies including complementary and integrative health approaches are strongly encouraged. For basic research, studies investigating pain processing in clinically relevant organ systems in animal models or human subjects are particularly encouraged.

2) Basic and Mechanistic Understanding of Myofascial Pain. Pain associated with myofascial tissues is among the most common types of chronic pain. Contrary to the conventional wisdom, evidence is emerging that fascia tissues are heavily innervated, but little research is underway to ascertain the interactions between fascia and other tissues involved in pain sensation. Understanding the mechanisms underlying the neuronal innervation of fascia as well as muscles may help uncover novel therapeutic targets for pain management. Exploratory studies to develop preclinical models to study myofascial pain, gain novel understanding of pain pathophysiology involving myofascial tissues, and develop novel therapeutic targets and non-opioid or non-pharmacological therapies for myofascial pain are particularly encouraged.

3) Fundamental Science of Biophysical Force-Based Interventions to Prevent or Manage Chronic Pain. Biophysical force-based interventions, such as massage, acupuncture, chiropractic manipulations, osteopathic treatments, represent non-pharmacological pain management paradigms commonly used by the general public with little scientific insights and evidence. The 2021 Nobel Prize for Physiology and Medicine was awarded, in part, for the discovery of the first mechanoreceptor, the protein in our body to detect the external biophysical force or pressure. Exploratory studies that will build on the exciting and transformative discovery to study the fundamental science of how biophysical force-based interventions may regulate pain related processes or targets in preclinical systems or clinical populations are particularly encouraged.

4) Identifying Novel Therapeutic Targets of Pain for Non-Addictive Natural Products. Natural products, including metabolites products by plants, animals, and microbes, have historically been the sources of many modern medicines. One of the 2021 Nobel Prize for Physiology and Medicine recipients was awarded for the identification of a novel pain receptor in response to the natural product, chili pepper, and is a great example of the importance of searching for novel pain therapeutic targets in response to non-addictive natural products. The following exploratory studies or efforts are strongly encouraged:

a) early phase preclinical exploratory natural product discovery for pain including analgesic, nociceptive, and proprioceptive targets

b) screening of natural product libraries against known or novel targets relevant to pain

c) collection or resupply (e.g., fermentation, cultivation, harvest, extraction, purification, synthesis) of known analgesic natural products for further evaluation

d) mining of existing literature, pharmacopeias, and ancient texts for candidate analgesic natural products worthy of further consideration using modern research methodologies

5) The Science of Music Therapies to Enhance Pain Management. Music and music therapies have often been used by the public and health care centers or hospitals to help relieve pain and soothe the patients. However, little is known about how and why music-based interventions could help with pain relief and how we could optimize their pain-relief effects. Innovative exploratory studies to understand the fundamental science underlying music's power for pain relief or support clinical research to optimize and enhance music's therapeutic effects for pain are particularly encouraged.

6) Multi-Component Pain Management Intervention Development. Research has demonstrated that some mind and body therapies are effective at improving pain outcomes. While these therapies have shown promise, the efficacy of any single-modality treatment is typically modest, and finding a way to enhance the effect size of clinical outcomes is a crucially important goal. Multicomponent strategies may enhance the benefit to individuals by simultaneously targeting multiple pathways and may be more effective than a treatment used in isolation. To achieve generalizable results from trials, it is important to have a reproducible multicomponent intervention or algorithm of care that can be consistently delivered by different clinicians at different sites to conduct multisite trials to assess efficacy or effectiveness. Studies to develop and/or iteratively refine reproducible treatment protocols for multicomponent interventions for the management of pain are encouraged, which may use Delphi panels, computational modeling, or other methods. Studies to assess the acceptability or adherence to a protocolized multicomponent interventions that include complementary or integrative approaches for the management of pain.