Pain
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Chemotherapy-induced neuropathic pain (CINP) in both sexes compromises many current chemotherapeutics and lacks a FDA-approved therapy. We recently identified the sphingosine-1-phosphate receptor subtype 1 (S1PR1) and A3 adenosine receptor subtype (A3AR) as novel targets for therapeutic intervention. Our work in male rodents using paclitaxel, oxaliplatin and bortezomib showed robust inhibition of CINP with either S1PR1 antagonists or A3AR agonists. ⋯ Morphine and duloxetine, both clinical analgesics, reversed BINP in female mice, demonstrating that the lack of response is specific to S1PR1 and A3AR agents. Our findings suggest that A3AR- and S1PR1-based therapies are not viable approaches in preventing and treating BINP in females and should inform future clinical trials of these drugs as adjuncts to chemotherapy. We have found that there are sexually dimorphic responses to S1PR1 antagonists and A3AR agonists for the treatment of bortezomib-induced neuropathic pain.
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Sickle cell disease (SCD) is a medical condition in which chronic pain is common and negatively impacts psychosocial function and quality of life. Although the brain mechanisms underlying chronic pain are well studied in other painful conditions, the brain mechanisms underlying chronic pain and the associated psychosocial comorbidities are not well established in SCD. A growing literature demonstrates the effect of treatment of chronic pain, including pharmacological and nonpharmacological treatments, on brain function. ⋯ Although neuroimaging studies show an important role for psychological factors, pain management is nearly exclusively based on opioids. Behavior therapy seems useful to improve psychological symptoms as well as chronic pain and quality of life. Further investigation is required with larger cohorts, matched controls, and examination of treatment-related neural mechanisms.
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Migraine is a debilitating condition; however, the pharmacological effects on central nervous system networks after successful therapy are poorly understood. Defining this neurocircuitry is critical to our understanding of the disorder and for the development of antimigraine drugs. ⋯ Whole-brain analysis yielded significant between-group (inflammatory soup vs synthetic interstitial fluid) alterations in functional connectivity across the cerebellar, default mode, basal ganglia, autonomic, and salience networks. These results demonstrate the large-scale antimigraine effects of sumatriptan-naproxen co-administration after dural sensitization.
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Comorbidity of pain and posttraumatic stress disorder is well recognized, but the reason for this association is unclear. This study investigated the direction of the relationship between pain and traumatic stress and the role that pain-related fear plays, for patients with acute whiplash-associated disorder. Participants (n = 99) used an electronic diary to record hourly ratings of pain, traumatic stress, and fear of pain (FOP) symptoms over a day. ⋯ Differences between this study and others that reported mutual maintenance can be understood in terms of different stages of whiplash-associated disorder and different intervals between repeated measurements. Traumatic stress may affect pain over longer time intervals than measured in this study. Future research could explore how relationships between traumatic stress symptoms, pain, and FOP change over time, and whether previous experiences of traumatic stress influence these relationships.