Pain
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Chronic pain remains poorly managed. The integration of immersive technologies (ie, virtual reality [VR]) with neuroscience-based principles may provide effective pain treatment by targeting cognitive and affective neural processes that maintain pain and therefore potentially changing neurobiological circuits associated with pain chronification and amplification. We tested the effectiveness of a novel VR neuroscience-based therapy (VRNT) to improve pain-related outcomes in n = 31 participants with chronic back pain, evaluated against usual care (waitlist control; n = 30) in a 2-arm randomized clinical trial (NCT04468074). ⋯ Several secondary clinical outcomes were also improved by VRNT, including disability, quality of life, sleep, and fatigue. In addition, VRNT was associated with increases in dorsomedial prefrontal functional connectivity with the superior somatomotor, anterior prefrontal and visual cortices, and decreased white matter fractional anisotropy in the corpus callosum adjacent to the anterior cingulate, relative to the control condition. Thus, VRNT showed preliminary efficacy in significantly reducing pain and improving overall functioning, possibly through changes in somatosensory and prefrontal brain networks.
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Pain science education (PSE) provides people with an understanding of "how pain works" grounded in the biopsychosocial model of pain; it has been demonstrated to improve outcomes in musculoskeletal pain conditions. Preliminary evidence suggests PSE may be effective for female individuals with persistent pelvic pain, but how the content of PSE needs to be modified for this group remains to be determined. A reflexive thematic analysis of qualitative data was performed to identify PSE concepts that female individuals with persistent pelvic pain consider important and why. ⋯ Most participants had been diagnosed with endometriosis (n = 16). Four themes were generated capturing PSE concepts considered important by female individuals with "improved" pelvic pain: (1) "A sensitised nervous system leads to overprotective pain" validated their pelvic pain as being real; (2) "Pain does not have to mean the body is damaged (although sometimes it does)" provided reassurance that pelvic pain does not mean their condition is worsening; (3) "How I think, feel, and 'see' my pain can make it worse" enabled participants to find optimal ways to manage their pain; and (4) "I can change my pain… slowly" provided hope that pelvic pain can improve and empowered them to pursue pain improvement as a viable goal. This study generated 4 PSE learning concepts that were important to female individuals with improved pelvic pain and may be incorporated into PSE curricula for female individuals with pelvic pain.
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Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 μg) induced short-term (<24 hours) mechanical allodynia and heat hyperalgesia, a response that is compromised in Tlr7-/- or Trpa1-/- mice. Ex vivo and in vivo calcium imaging in GCaMP6-report mice revealed increased calcium signal in spinal cord afferent terminals and doral root ganglion/dorsal root ganglia neurons following spinal perfusion and intraplantar injection of let-7b. ⋯ The high dose of let-7b also induced microgliosis in the spinal cord. Of interest, intrathecal minocycline only inhibited let-7b-induced mechanical allodynia in male but not female mice. Our findings indicate that the secreted microRNA let-7b has the capacity to provoke pain through both neuronal and glial signaling, thereby establishing miRNA as an emerging neuromodulator.
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Opioids are commonly prescribed to patients with chronic pain. Chronic opioid usage comes with a slew of serious side effects, including opioid-induced hyperalgesia (OIH). The patients with long-term opioid treatment experience paradoxical increases in nociceptive hypersensitivity, namely, OIH. ⋯ More importantly, we show that supplementation with short-chain fatty acids (butyrate, propionate, and acetate) can delay the onset of OIH, indicating that short-chain fatty acids play a direct role in the development of OIH. Our findings suggest that gut microbiome could be targeted to treat OIH, and the ketogenic diet can be used as a complementary approach for pain relief in patients with chronic opioid treatment. We only used male mice in this study, and thus, our findings cannot be generalized to both sexes.