Pain
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The high frequency stimulation (HFS) model can be used alongside quantitative sensory testing (QST) to assess the sensitisation of central nociceptive pathways. However, the validity and between-session reliability of using QST z -score profiles to measure changes in mechanical and thermal afferent pathways in the HFS model are poorly understood. In this study, 32 healthy participants underwent QST before and after HFS (5× 100 Hz trains; 10× electrical detection threshold) in the same heterotopic skin area across 2 repeated sessions. ⋯ There was no change in cold pain threshold (CPT) and heat pain threshold (HPT) z -score profiles across session 1 and 2, which were associated with moderate and good reliability, respectively. There were inconsistent changes in the sensitivity to innocuous thermal QST parameters, with cool detection threshold (CDT), warm detection threshold (WDT), and thermal sensory limen (TSL) all producing poor reliability. These data suggest that HFS-induced changes in MPS z -score profiles is a reliable way to assess experimentally induced central sensitisation and associated secondary mechanical hyperalgesia in healthy participants.
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The Center for Disease Control and Prevention estimates that 75% of reported cases of traumatic brain injury (TBI) are mild, where chronic pain and depression are 2 of the most common symptoms. In this study, we used a murine model of repeated mild TBI to characterize the associated pain hypersensitivity and affective-like behavior and to what extent microglial reactivity contributes to these behavioral phenotypes. Male and female C57BL/6J mice underwent sham or repeated mild traumatic brain injury (rmTBI) and were tested for up to 9 weeks postinjury, where an anti-inflammatory/neuroprotective drug (minocycline) was introduced at 5 weeks postinjury in the drinking water. ⋯ Finally, we show that the antiepileptic drug, gabapentin, produced negative reinforcement in male rmTBI mice that was prevented by minocycline treatment, whereas rmTBI female mice showed a place aversion to gabapentin. Collectively, pain hypersensitivity, increased tonic-aversive pain components, and negative affective states were evident in both male and female rmTBI mice, but suppression of microglial reactivity was only sufficient to reverse behavioral changes in male mice. Neuroinflammation in limbic structures seems to be a contributing factor in behavioral changes resulting from rmTBI.
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Randomized Controlled Trial Multicenter Study
Comparison of the analgesic effects of "superficial" and "deep" repetitive transcranial magnetic stimulation in patients with central neuropathic pain: a randomized sham-controlled multicenter international crossover study.
We directly compared the analgesic effects of "superficial" and 'deep" repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in patients with central neuropathic pain. Fifty-nine consecutive patients were randomly assigned to active or sham "superficial" (using a figure-of-8 [F8]-coil) or "deep" (using a Hesed [H]-coil) stimulation according to a double-blind crossover design. Each treatment period consisted of 5 daily stimulation sessions and 2 follow-up visits at 1 and 3 weeks after the last stimulation session. ⋯ The analgesic effects of both types of coils had a similar magnitude but were only moderately correlated ( r = 0.39, P = 0.02). The effects of F8-coil stimulation appeared earlier, whereas the effects of H-coil stimulation were delayed, but tended to last longer (up to 3 weeks) as regards to several secondary outcomes (PGIC and total NPSI score). In conclusion, "deep" and "superficial" rTMS induced analgesic effects of similar magnitude in patients with central pain, which may involve different mechanisms of action.
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People with chronic pain tend to interpret ambiguous information as health-related, more so than people without. In this study, we aimed to investigate whether people with rheumatoid arthritis (RA) exhibit this interpretation bias and whether it is associated with fear of disease progression (FoP). The interpretation biases of people with RA (n = 164) were compared with an age- and gender-matched control group. ⋯ We did not find evidence to suggest interpretation bias moderated the relationship between pain and FoP or that FoP added to the variance of other known predictors. Our results indicate that interpretation bias is common amongst people with RA and is associated with FoP. Further research is required to illuminate the exact nature of this relationship.
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The past 20 years have seen a dramatic shift in our understanding of the role of the immune system in initiating and maintaining pain. Myeloid cells, including macrophages, dendritic cells, Langerhans cells, and mast cells, are increasingly implicated in bidirectional interactions with nerve fibres in rodent pain models. However, our understanding of the human setting is still poor. ⋯ The directionality of results between studies was inconsistent, although the clearest pattern was an increase in macrophage frequency across conditions, phases, and tissues. Myeloid cell definitions were often outdated and lacked correspondence with the stated cell types of interest; overreliance on morphology and traditional structural markers gave limited insight into the functional characteristics of investigated cells. We therefore critically reappraise the existing literature considering contemporary myeloid cell biology and advocate for the application of established and emerging high-dimensional proteomic and transcriptomic single-cell technologies to clarify the role of specific neuroimmune interactions in chronic pain.