Pain
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Increased sensory sensitivity across non-nociceptive modalities is a common symptom of chronic pain conditions and is associated with chronic pain development. Providing a better understanding of the brain-behavior relationships that underlie multimodal hypersensitivity (MMH) may clarify the role of MMH in the development of chronic pain. We studied sensory hypersensitivity in a cohort of women (n = 147) who had diary confirmation of menstrual status and were enriched with risk factors for chronic pelvic pain, such as dysmenorrhea and increased bladder sensitivity. ⋯ These results demonstrate that activity in the primary visual cortex is not greater in individuals with greater visceral sensitivity. We hypothesize that downstream interpretation or integration of this signal is amplified in individuals with visceral hypersensitivity. Future studies aimed at reducing MMH in chronic pain conditions should prioritize targeting of cortical mechanisms responsible for aberrant downstream sensory integration.
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Facial expressions of pain have been identified in several animal species. The aim of this systematic review was to provide evidence on the measurement properties of grimace scales for pain assessment. The protocol was registered (SyRF#21-November-2019), and the study is reported according to the PRISMA guidelines. ⋯ Reliability and other forms of validity have been understudied. This systematic review identified gaps in knowledge on the measurement properties of grimace scales. Further studies should focus on improving psychometric testing, instrument refinement, and the use of grimace scales for pain assessment in nonhuman mammals.
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A commonly held belief suggests that turning one's attention away from pain reduces it, whereas paying attention to pain increases it. However, some attention-based therapeutic strategies for pain, such as mindfulness-based interventions, suggest that paying attention to painful stimuli can reduce pain, resulting in seemingly contradictory conclusions regarding attention and pain. ⋯ The analgesic effects of paying attention to painful stimuli were mediated by the primary somatosensory cortex and goal-directed attention regions in the prefrontal and parietal cortex. These findings suggest that suppressing early somatosensory processing through top-down modulation is the key mechanism of the analgesic effects of paying attention to painful stimuli, providing evidence that pain itself can be used as a component of pain management.
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IMT504, a noncoding, non-CpG oligodeoxynucleotide, modulates pain-like behavior in rats undergoing peripheral nerve injury, through mechanisms that remain poorly characterized. Here, we chose the spared nerve injury model in rats to analyze the contribution of mesenchymal stem cells (MSCs) in the mechanisms of action of IMT504. We show that a single subcutaneous administration of IMT504 reverses mechanical and cold allodynia for at least 5 weeks posttreatment. ⋯ Interestingly, the sole exposure of injured nerves to IMT504 also resulted in downregulated Tnf-α and Il-1β transcripts. Altogether, we reveal for the first time a direct association between the antiallodynic actions of IMT504, its promigratory and cytokine secretion modulating effects on MSCs, and further anti-inflammatory actions at injured nerves. The recapitulation of key outcomes in human MSCs supports the translational potential of IMT504 as a novel treatment for neuropathic pain with a unique mechanism of action involving the regulation of neuroimmune interactions.
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Voltage-gated calcium channels in sensory neurons underlie processes ranging from neurotransmitter release to gene expression and remain a therapeutic target for the treatment of pain. Yet virtually all we know about voltage-gated calcium channels has been obtained through the study of rodent sensory neurons and heterologously expressed channels. ⋯ However, HVA currents in human neurons differed from those in the rat in at least 3 potentially important ways: (1) Ca2+ current density was significantly smaller, (2) the proportion of nifedipine-sensitive currents was far greater, and (3) a subpopulation of human neurons displayed relatively large constitutive current inhibition. These results highlight the need to for the study of native proteins in their native environment before initiating costly clinical trials.