Pain
-
Communication within the brain is dynamic. Chronic pain can also be dynamic, with varying intensities experienced over time. Little is known of how brain dynamics are disrupted in chronic pain, or relates to patients' pain assessed at various timescales (eg, short-term state vs long-term trait). ⋯ Furthermore, greater dynamic connectivity with executive control networks was associated with milder NP, but greater dynamic connectivity with limbic networks was associated with greater NP. Compared with healthy individuals, the dFC features most highly related to trait NP were also more abnormal in patients with greater pain. Our findings indicate that dFC reflects patients' overall pain condition (ie, trait pain), not just their current state, and is impacted by complexities in pain features beyond intensity.
-
Microglia-neuron signalling in the spinal cord is a key mediator of mechanical allodynia caused by peripheral nerve injury. We recently reported sex differences in microglia in pain signalling in mice: spinal mechanisms underlying nerve injury-induced allodynia are microglial dependent in male but not female mice. Whether this sex difference in pain hypersensitivity mechanisms is conserved in other species is unknown. ⋯ Furthermore, chromatin immunoprecipitation-qPCR revealed that the transcription factor IRF5 differentially binds to the P2rx4 promoter region in female rats vs male rats. Finally, mechanical allodynia was produced in otherwise naive rats by intrathecally administering P2X4R-stimulated microglia from male rats but not those from female rats. Together, our findings demonstrate the existence of sexually dimorphic pain signalling in rats, suggesting that this sex difference is evolutionarily conserved, at least across rodent species.
-
In knee osteoarthritis (OA), pain sensitization has been linked to a more severe symptomatology, but the prognostic implications of pain sensitivity in people undergoing conservative treatment such as physiotherapy are not established. This study aimed to prospectively investigate the association between features of pain sensitization and clinical outcome (nonresponse) after guideline-based physiotherapy in people with knee OA. Participants (n = 156) with moderate/severe knee OA were recruited from secondary care. ⋯ The model demonstrated high sensitivity (87.8%) but modest specificity (52.3%). The independent relationship between pain sensitization and nonresponse may indicate an underlying explanatory association between neuroplastic changes in nociceptive processing and the maintenance of ongoing pain and disability in knee OA pain. These preliminary results suggest that interventions targeting pain sensitization may warrant future investigation in this population.
-
Sensory disturbances often spread beyond the site of injury in complex regional pain syndrome (CRPS) but whether this applies equally to CRPS I and II, or changes across the course of the disease, is unknown. Establishing this is important, because different symptom profiles in CRPS I and II, or in acute vs chronic CRPS, might infer different pathophysiology and treatment approaches. To explore these questions, sensory disturbances were assessed in the limbs and forehead of 71 patients with CRPS I and 33 patients with CRPS II. ⋯ Some of these hemisensory disturbances strengthened with chronicity of pain. These findings suggest that heightened excitability of nociceptive pathways in CRPS spreads to hemisensory convergence points in the brainstem or higher brain centres, possibly in association with compromised pain controls. The similarity of symptom profiles in chronic CRPS I and II implies shared mechanisms despite different triggers.