Quantitative sensory testing (QST) is a useful tool in evaluating patients with neuropathic pain. In light of the COVID-19 pandemic and taking into consideration the transportation barriers that many chronic pain patients face, there is an increasing need for a valid QST protocol that can be completed at home. This study sought to establish and validate an at-home QST protocol for the evaluation of patients with neuropathic pain. A sample of 18 patients with neuropathic pain who had previously completed the validated bedside QST protocol completed the at-home QST assessment and a series of questionnaires. Bivariate correlations between in person and at home QST measures were assessed using Pearson correlations, and Spearman's rho was applied when variables showed non-normal distributions. Results found that comparable at home QST protocols included punctate hyperalgesia, cold allodynia, cold hyperalgesia, and the cold pain tolerance-time measure. At home tests that did not show strong correlations with previously established beside QST included static mechanical allodynia, dynamic mechanical allodynia, temporal summation of mechanical pain, and the cold pain tolerance- pain rating. This research will be instrumental in testing less mobile participants or those who cannot come to a laboratory site for traditional QST testing and future sensory phenotyping of patients that will move the field toward a more individualized medicine approach. / 2024-01-28T00:00:00Z

Chronic neuropathic pain is a leading cause of disability worldwide and is associated with immense economic burden. Of all chronic neuropathic pain conditions, chemotherapy-induced peripheral neuropathy (CIPN) persists as a monumental public health crisis, as it is the most common comorbidity among those receiving chemotherapy for cancer treatment. CIPN is unique compared to other forms of neuropathic pain in that it is severely dose-limiting, often leading to disruption or cessation of chemotherapeutic treatment and complicating an individual’s cancer prognosis. Current pharmacological treatments for combatting CIPN are widespread yet are all accompanied with the same hindrances – they are limited in therapeutic efficacy when administered chronically and are associated with severe risk for adverse effects. Therefore, there is a clear unmet need for novel pharmacotherapies for CIPN that achieve strong therapeutic efficacy while minimizing the susceptibility to adverse events.Here, we characterize the therapeutic efficacy and pharmacological mechanisms of a novel, plant-derived alkaloid mitragynine (MG), a constituent of the kratom plant (Mitragyna speciosa) in a mouse model of CIPN. Kratom products have emerged in the US in recent years as a popular form of self-treating pain, opioid withdrawal, and symptoms of anxiety and depression, but these intended uses are largely based on anecdotal reports in humans. MG possesses a unique, mixed pharmacological profile combining opioid, adrenergic, and serotonergic properties – resembling the pharmacology of current CIPN pharmacotherapies such as antidepressants. However, the relation of these pharmacological mechanisms of MG to the context of CIPN remain under characterized. Kratom products are also commonly used in combination with cannabis products, which are also used for self-treating pain, and play a significant role in palliative care for terminal cancer patients. Yet, interactions between kratom alkaloids and cannabinoid signaling have yet to be studied in the context of CIPN. Lastly, the basis of potential utility of individual kratom constituents such as MG on anxiety- and depression-like behaviors, which are heavily comorbid in individuals with CIPN, remain understudied. The present studies were conducted to explore the role of the kratom alkaloid MG on both pain and affective behaviors associated with CIPN, at the pharmacological, cellular, and molecular level. To accomplish this, we measured 1. Contributions of opioid and adrenergic signaling mechanisms to the therapeutic efficacy of MG in a mouse model of oxaliplatin-induced mechanical hypersensitivity using pharmacological inhibition. 2. Contributions of cannabinoid signaling to the therapeutic efficacy of MG in a mouse model of oxaliplatin-induced mechanical hypersensitivity and inflammatory pain using pharmacological and genetic approaches. 3. Effects of MG on affective behaviors associated with CIPN using mouse models of the tail-suspension test, elevated zero maze, and conditioned place preference. Overall, the findings from this dissertation support the hypothesis that MG displays therapeutic efficacy against nocifensive behavior of CIPN and pain-related affective behaviors. Opioid, adrenergic, and cannabinoid mechanisms all contribute to the effect of MG on oxaliplatin-induced mechanical hypersensitivity. MG is also capable of normalizing aberrant neurotrophic factor signaling associated with CIPN. Lastly, MG produces anxiolytic effects when repeatedly administered without developing a conditioned place preference, suggesting that it achieves therapeutic efficacy in a model of CIPN without risk of adverse events. / Biomedical Sciences

Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. We investigated the effects of light-emitting diodes (LEDs), in the visible spectrum, on acute sensory thresholds in naive rats as well as in experimental neuropathic pain. Rats receiving green LED light (wavelength 525 nm, 8 h/d) showed significantly increased paw withdrawal latency to a noxious thermal stimulus; this antinociceptive effect persisted for 4 days after termination of last exposure without development of tolerance. No apparent side effects were noted and motor performance was not impaired. Despite LED exposure, opaque contact lenses prevented antinociception. Rats fitted with green contact lenses exposed to room light exhibited antinociception arguing for a role of the visual system. Antinociception was not due to stress/anxiety but likely due to increased enkephalins expression in the spinal cord. Naloxone reversed the antinociception, suggesting involvement of central opioid circuits. Rostral ventromedial medulla inactivation prevented expression of light-induced antinociception suggesting engagement of descending inhibition. Green LED exposure also reversed thermal and mechanical hyperalgesia in rats with spinal nerve ligation. Pharmacological and proteomic profiling of dorsal root ganglion neurons from green LED-exposed rats identified changes in calcium channel activity, including a decrease in the N-type (CaV2.2) channel, a primary analgesic target. Thus, green LED therapy may represent a novel, nonpharmacological approach for managing pain.