Pain
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Randomized Controlled Trial
Referred sensation location can be altered by a strong heterotopic nociceptive stimulus: Implications for clinical pain conditions.
Referred sensations (RS) are a common clinical phenomenon in patients with musculoskeletal pain; however, the underlying mechanisms of RS and implications for diagnosis and management are poorly understood. The location of referral seems to have a preferred site, but studies have suggested it can be redirected to a site of previous injury and pain. However, it is not known if the same phenomenon can occur for a much shorter-lasting painful stimulus in the trigeminal system. ⋯ However, the RS location was displaced on average 1.2 cm between the baseline and postinfusion assessments for the hypertonic saline infusion, which was significantly increased when compared with the isotonic saline infusion which was on average 0.4 cm. These novel findings indicate the potential to modify the location of RS in the trigeminal system following a relatively brief noxious input. Clinicians need to be aware of the possible rerouting of RS in patients with complex orofacial pain.
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Open-label placebos, or placebos without deception, have been found to induce analgesia, a challenging concept that need to be investigated in detail. In particular, what we need to know is the mechanism through which analgesia is induced when no deception is involved. In this study, we show for the first time that open-label placebo analgesia can be reversed by the opioid antagonist naloxone, as already shown for deceptive placebos. ⋯ In these responders, we found that a hidden injection of 10 mg naloxone could reverse placebo analgesia compared with a hidden injection of saline solution. At least 2 control groups showed that naloxone per se was not hyperalgesic, thus ruling out naloxone-induced hyperalgesia as a confounding variable. In light of the need to better understand open-label placebo effects, these findings represent the first experimental evidence that nondeceptive placebo analgesia may be mediated by the same mechanisms as deceptive placebo analgesia, namely the endogenous opioid systems.
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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the multidisciplinary approach to the study of chronic pelvic pain research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more severe symptoms, yet the neurobiological correlates of this subtype are largely unknown. We previously showed that ex vivo toll-like receptor 4 (TLR4) cytokine/chemokine release is associated with the presence of COPCs, as well as widespread pain and experimental pain sensitivity women with IC/BPS. ⋯ Controlling for patient age, body mass index, and site of collection, we found that greater ex vivo TLR4-stimulated cytokine/chemokine release was associated with the presence of COPCs ( P < 0.01), extent of widespread pain ( P < 0.05), but not experimental pain sensitivity ( P > 0.05). However, a second component of anti-inflammatory, regulatory, and chemotactic activity was associated with reduced pain sensitivity ( P < 0.01). These results confirm that the IC/BPS + COPCs subtype show higher levels of ex vivo TLR4 cytokine/chemokine release and support a link between immune priming and nociplastic pain in IC/BPS.
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Temporomandibular disorders (TMD) include a group of musculoskeletal disorders that may involve increased responsiveness of nociceptive neurons in the central nervous system (ie, central sensitization). To test this hypothesis further, this study examined whether, as compared with healthy subjects, patients with chronic TMD have a greater propensity to develop secondary mechanical hyperalgesia-a phenomenon that can be confidently attributed to central sensitization. In this case-control study, we assessed the area of secondary mechanical hyperalgesia induced experimentally by delivering high-frequency electrical stimulation (HFS) to the volar forearm skin in 20 participants with chronic TMD and 20 matched healthy controls. ⋯ Regarding secondary outcomes, there was no group difference in the intensity of secondary mechanical hyperalgesia, but allodynia to cotton after HFS was more frequent in the chronic TMD group. To the best of our knowledge, this is the first study to show that individuals with chronic TMD have an increased propensity to develop secondary hyperalgesia in a site innervated extratrigeminally. Our results contribute to a better understanding of the pathophysiology of chronic TMD.
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Complex regional pain syndrome (CRPS) is characterized by inflammation and a failure of multimodal signal integration in the central nervous system (CNS). Central nervous system reorganization might account for sensory deficits, pain, and motor symptoms in CRPS, but it is not clear how motor control is affected by CNS mechanisms. The present study characterized the motor performance and related cortical activity of 16 CRPS patients and 16 control participants during the planning of visually guided unimanual grips, in patients with either the unaffected left or the affected right hand, and investigated resting-state sensorimotor coupling in MRI. ⋯ Fear of movement or individual pain scores contributed only marginally to the observed effects. The study suggests that changes in planning-related sensorimotor CNS regions may explain difficulties with force exertion and motor control in CRPS. Perspective : Functional changes in motor planning-related brain regions might indicate that feedback-enhanced functional motor training may be effective for CRPS rehabilitation.