Pain
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Neural mechanisms mediating the transition from acute to chronic pain remain largely unknown. In a longitudinal brain imaging study, we followed up patients with a single sub-acute back pain (SBP) episode for more than 1 year as their pain recovered (SBPr), or persisted (SBPp) representing a transition to chronic pain. We discovered brain white matter structural abnormalities (n=24 SBP patients; SBPp=12 and SBPr=12), as measured by diffusion tensor imaging (DTI), at entry into the study in SBPp in comparison to SBPr. ⋯ Tractography analysis indicated that abnormal regional FA was linked to differential structural connectivity to medial vs lateral prefrontal cortex. Local FA was correlated with functional connectivity between medial prefrontal cortex and nucleus accumbens in SBPr. As we have earlier shown that the latter functional connectivity accurately predicts transition to chronic pain, we can conclude that brain structural differences, most likely existing before the back pain-inciting event and independent of the back pain, predispose subjects to pain chronification.
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Recent studies have indicated an important role of chemokines such as CCL2 in the development of chronic pain. However, the distinct roles of different chemokines in the development and maintenance of neuropathic pain and in their interactions with neurons have not been clearly elucidated. We found that spinal nerve ligation (SNL) not only induced persistent neuropathic pain symptoms, including mechanical allodynia and heat hyperalgesia, but also produced sustained CXCL1 upregulation in the spinal cord. ⋯ SB225002 also attenuated SNL-induced pain hypersensitivity. Collectively, our results have demonstrated a novel form of chemokine-mediated glial-neuronal interaction in the spinal cord that can drive neuropathic pain. Inhibition of the CXCL1-CXCR2 signaling may offer a new therapy for neuropathic pain management.
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Growing evidence suggests that leukocyte extravasation is initiated by the interaction of selectins with their ligands; as well as an essential role for P-selectin in the initial recruitment of inflammatory cells to sites of inflammation. In this study, P-selectin-deficient (P-sel-/-) mice were used to test the hypothesis that lack of P-selectin would attenuate the recruitment of inflammatory cells to the site of inflammation, thereby modulating pain in a murine chronic neuropathic pain model. Nociceptive sensitization and the microenvironment of the peripheral injury site were studied in wild-type (P-sel+/+) and P-selectin-deficient (P-sel-/-) mice after partial sciatic nerve ligation (PSNL). ⋯ In addition, endogenous opioid peptides mRNA was significantly lower in P-sel-/- mice compared with P-sel +/+ mice. The current results demonstrated that the absence of P-selectin in mice leads to an altered microenvironment that attenuated behavioral hypersensitivity. The specific role of P-selectin could have been a result of decreased neutrophils, as well as the accumulation of macrophages at the site of injury, which may subsequently modulate the inflammatory cytokine expression and impact behavioral hypersensitivity within the injured nerve.
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Randomized Controlled Trial
Longstanding neuropathic pain after spinal cord injury is refractory to transcranial direct current stimulation: A randomized controlled trial.
Neuropathic pain remains one of the most difficult consequences of spinal cord injury (SCI) to manage. It is a major cause of suffering and adds to the physical, emotional, and societal impact of the injury. Despite the use of the best available treatments, two thirds of people experiencing neuropathic pain after SCI do not achieve satisfactory pain relief. ⋯ A similar lack of effect was also seen after sham treatment. Because the injury duration in this study was significantly greater than that of previous investigations, it is possible that tDCS is an effective analgesic only in individuals with relatively recent injuries and pain. Future investigations comparing a range of injury durations are required if we are to determine whether this is indeed the case.
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The current study applied a model of pain communication to examine the distinction between verbal and nonverbal pain expression in their prediction of punishing, empathic, and solicitous spouse responses to patient pain. It was hypothesized that on days when patients engaged in more nonverbal expression, spouses would respond more positively (ie, with less punishing and more solicitous and empathic behavior). The same pattern was predicted for verbal expression. ⋯ The predicted positive main effect of nonverbal expression on empathic and solicitous responses was supported by the data, as was the positive main effect for verbal pain expression. Results from moderation analyses partially supported our hypothesis in that patients' nonverbal pain expression was even more strongly related to empathic and solicitous spouse responses on days of high verbal pain expression, and patients were buffered from spouse punishing responses on days when both nonverbal and verbal expression were high. These findings suggest that pain expression in both verbal and nonverbal modes of communication is important for positive and negative spousal responses.