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Pain catastrophizing has been identified as a prognostic indicator of poor outcome following knee arthroplasty. Interventions to address pain catastrophizing, to our knowledge, have not been tested in patients undergoing knee arthroplasty. The purpose of this study was to determine whether pain coping skills training in persons with moderate to high pain catastrophizing undergoing knee arthroplasty improves outcomes 12 months postoperatively compared with usual care or arthritis education.
Learn More >Mast cells can be found in close proximity to peripheral nerve endings where, upon activation, they release a broad range of pro-inflammatory cytokines and chemokines. However, the precise mechanism underlying this so-called neurogenic inflammation and associated pain has remained elusive. Here we report that the mast-cell-specific receptor Mrgprb2 mediates inflammatory mechanical and thermal hyperalgesia and is required for recruitment of innate immune cells at the injury site. We also found that the neuropeptide substance P (SP), an endogenous agonist of Mrgprb2, facilitates immune cells' migration via Mrgprb2. Furthermore, SP activation of the human mast cell led to the release of multiple pro-inflammatory cytokines and chemokines via the human homolog MRGPRX2. Surprisingly, the SP-mediated inflammatory responses were independent of its canonical receptor, neurokinin-1 receptor (NK-1R). These results identify Mrgprb2/X2 as an important neuroimmune modulator and a potential target for treating inflammatory pain.
Learn More >Ecological momentary assessment (EMA) involves repeated sampling of people's current experiences in real time in their natural environments, which offers a granular perspective on patients' experience of pain and other symptoms. However, EMA can be burdensome to patients, and its benefits depend upon patients' engagement in the assessments.
Learn More >Differentiation between self-produced tactile stimuli and touch by others is necessary for social interactions and for a coherent concept of "self." The mechanisms underlying this distinction are unknown. Here, we investigated the distinction between self- and other-produced light touch in healthy volunteers using three different approaches: fMRI, behavioral testing, and somatosensory-evoked potentials (SEPs) at spinal and cortical levels. Using fMRI, we found self-other differentiation in somatosensory and sociocognitive areas. Other-touch was related to activation in several areas, including somatosensory cortex, insula, superior temporal gyrus, supramarginal gyrus, striatum, amygdala, cerebellum, and prefrontal cortex. During self-touch, we instead found deactivation in insula, anterior cingulate cortex, superior temporal gyrus, amygdala, parahippocampal gyrus, and prefrontal areas. Deactivation extended into brain areas encoding low-level sensory representations, including thalamus and brainstem. These findings were replicated in a second cohort. During self-touch, the sensorimotor cortex was functionally connected to the insula, and the threshold for detection of an additional tactile stimulus was elevated. Differential encoding of self- vs. other-touch during fMRI correlated with the individual self-concept strength. In SEP, cortical amplitudes were reduced during self-touch, while latencies at cortical and spinal levels were faster for other-touch. We thus demonstrated a robust self-other distinction in brain areas related to somatosensory, social cognitive, and interoceptive processing. Signs of this distinction were evident at the spinal cord. Our results provide a framework for future studies in autism, schizophrenia, and emotionally unstable personality disorder, conditions where symptoms include social touch avoidance and poor self-vs.-other discrimination.
Learn More >Touch and mechanical pain represent distinct, but interactive, modalities of mechanosensation. However, the molecular mechanisms underlying these mechanotransduction processes remain incompletely understood. Here, we show that deletion of the mechanically activated and rapidly adapting Piezo2 channel in a portion of the low-threshold mechanoreceptors and a majority of the IB4-positive nociceptors impairs touch but sensitizes mechanical pain in mice. Ectopic expression of the Piezo2 homolog, the intermediately adapting Piezo1 channel, in sensory neurons can sensitize touch in normal mice and rescue defective touch of the Piezo2-knockout mice. Broad expression of Piezo1 in sensory neurons decreases, rather than evokes, mechanical pain responses. Together, our data suggest that Piezo channels can mediate touch and indirectly suppress acute pain. Tuning Piezo-mediated touch sensitivity allows us to recapitulate the inhibitory effect of touch on acute pain in mouse models.
Learn More >Nociceptors, sensory neurons that detect damage or potential damage to the body, are the first stage of communicating noxious stimuli from the periphery to central nervous system (CNS). In this study, long-term potentiation (LTP) in the CNS of the medicinal leech, Hirudo verbana, was examined, taking advantage of the ability to selectively record from nociceptive synapses in this model organism. High frequency stimulation (HFS) of nociceptors produced a persistent increase in synaptic transmission and this LTP was both NMDA receptor-mediated and synapse-specific. Surprisingly, inhibition of NMDA receptors during HFS "uncovered" a persistent form of depression. This long-term depression (LTD) was mediated by the endocannabinoid 2-arachidonoyl glycerol (2-AG) acting on a TRPV (transient receptor potential vanilloid) -like channel. These observations suggest that (1) NMDA receptor mediated LTP is observed in nociceptors across both vertebrate and invertebrate phyla and (2) there may be an interaction between NMDA receptor-mediated and endocannabinoid-mediated forms of synaptic plasticity in nociceptors. Specifically, the NMDA receptor mediated processes may suppress endocannabinoid signaling. Such findings could be significant for understanding cellular mechanisms behind nociceptive sensitization and perhaps their contribution to chronic pain.
Learn More >Anti-citrullinated protein antibodies (ACPA) have been suggested to have a potential role in both bone loss and pain in rheumatoid arthritis (RA), based on studies in vitro and in animal models. Here we addressed if anti-cyclic citrullinated (anti-CCP) antibodies were associated with osteopenia or pain in patients with RA, at the time for diagnosis.
Learn More >Many neuropsychological theories agree that the brain maintains a relatively persistent representation of one's own body, as indicated by vivid "phantom" experiences. It remains unclear how the loss of sensory and motor information contributes to the presence of this representation. Here, we focus on new empirical and theoretical evidence of phantom sensations following damage to or an anesthetic block of the brachial plexus. We suggest a crucial role of this structure in understanding the interaction between peripheral and central mechanisms in health and in pathology. Studies of brachial plexus function have shed new light on how neuroplasticity enables "somatotopic interferences", including pain and body awareness. Understanding the relations among clinical disorders, their neural substrate, and behavioral outcomes may enhance methods of sensory rehabilitation for phantom limbs.
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