Pain
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Randomized Controlled Trial
Biopsychosocial influence on shoulder pain: results from a randomized pre-clinical trial of exercise-induced muscle injury.
Prior cohort studies validated that a subgroup defined by a specific COMT genotype and pain catastrophizing is at increased risk for heightened responses to exercise-induced or surgically induced shoulder pain. In this clinical trial, we used our preclinical model of exercise-induced muscle injury and pain to test the efficacy of interventions matched to characteristics of this high-risk subgroup (ie, personalized medicine approach). Potential participants provided informed consent to be screened for eligibility based on subgroup membership and then, as appropriate, were enrolled into the trial. ⋯ Additional analyses found no differences between these intervention groups when shoulder pain duration was an outcome, and no differential treatment responses were detected based on sex, race, or level of pain catastrophizing. This trial indicates that these treatments were not efficacious for this high-risk subgroup when shoulder pain was induced by exercise-induced muscle injury. Accordingly, this phenotype should only be used for prognostic purposes until additional trials are completed in clinical populations.
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Randomized Controlled Trial
Disentangling self from pain: mindfulness meditation-induced pain relief is driven by thalamic-default mode network decoupling.
For millenniums, mindfulness was believed to diminish pain by reducing the influence of self-appraisals of noxious sensations. Today, mindfulness meditation is a highly popular and effective pain therapy that is believed to engage multiple, nonplacebo-related mechanisms to attenuate pain. Recent evidence suggests that mindfulness meditation-induced pain relief is associated with the engagement of unique cortico-thalamo-cortical nociceptive filtering mechanisms. ⋯ Preregistered (NCT03414138) whole-brain analyses revealed that mindfulness meditation-induced analgesia was moderated by greater thalamus-precuneus decoupling and ventromedial prefrontal deactivation, respectively, signifying a pain modulatory role across functionally distinct neural mechanisms supporting self-referential processing. Two separate preregistered seed-to-seed analyses found that mindfulness meditation-based pain relief was also associated with weaker contralateral thalamic connectivity with the prefrontal and primary somatosensory cortex, respectively. Thus, we propose that mindfulness meditation is associated with a novel self-referential nociceptive gating mechanism to reduce pain.
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The biopsychosocial model (BPS) of chronic pain aspires to be comprehensive, incorporating psychological and social factors omitted from biomedical models. Although psychosocial factors are viewed as highly influential in understanding behavioral and psychological responses to pain, these factors are usually viewed as modifiers of biological causes of the experience of pain itself, rather than as equal contributors to pain. To further advance the BPS model, we re-examine a classic 1994 article by Wilbert "Bill" Fordyce, "Pain and suffering: what is the unit?" In this article, Fordyce suggested that pain-related disability and suffering should be viewed as "transdermal," as having causes both inside and outside the body. ⋯ It makes it possible to place psychological and social factors on an equal footing with biological ones in explaining pain itself and to remove distinctions between pain mechanisms and pain meanings. The brain's salience network now offers a platform on which diverse influences on pain experience-from nociception to multisensory indicators of safety or danger-can be integrated, bridging the gap between impersonal nociceptive mechanisms and personal meanings. We also argue that Fordyce's article is practically important because this concept expands the BPS model beyond the bounds of the clinical encounter, opening the door to the full range of social, psychological, and biological interventions, empowering patients and nonmedical providers to tackle chronic pain.
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Neuropathic pain is a complex, debilitating disease that results from injury to the somatosensory nervous system. The presence of systemic chronic inflammation has been observed in patients with chronic pain but whether it plays a causative role remains unclear. This study aims to determine the perturbation of systemic homeostasis by an injury to peripheral nerve and its involvement in neuropathic pain. ⋯ Although transferring sham serum to naïve mice did not change their pain sensitivity, PSNL serum significantly lowered mechanical thresholds and induced cold hypersensitivity in naïve mice. With broad anti-inflammatory properties, bone marrow cell extracts not only partially restored serum proteomic homeostasis but also significantly ameliorated PSNL-induced mechanical allodynia, and serum from bone marrow cell extracts-treated PSNL mice no longer induced hypersensitivity in naïve mice. These findings clearly demonstrate that nerve injury has a long-lasting impact on systemic homeostasis, and nerve injury-associated systemic inflammation contributes to the development of neuropathic pain.
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Nociplastic pain conditions develop predominantly in women. We recently established a murine nociplastic pain model by applying postinjury thermal (40°C) stimulation to an injured (capsaicin-injected) area, triggering a transition to a nociplastic pain state manifesting as persistent mechanical hypersensitivity outside of the previously injured area. The nociplastic pain state was centrally maintained by spinal microglia in males but peripherally by ongoing afferent activity at the previously injured area in females. ⋯ At the previously injured area, afferents responsive to allyl isothiocyanate (AITC), a TRPA1 agonist, contributed to the maintenance of nociplastic mechanical hypersensitivity in gonad-intact females. In ex vivo skin-nerve preparations, only AITC-responsive afferents from the nociplastic pain model in gonad-intact females showed ongoing activities greater than control. These results suggest that gonadal hormones are critical for peripherally maintained nociplastic pain state in females by sensitizing AITC-responsive afferents to be persistently active.