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This prospective cohort study explored whether two distinguished sensory parameters predicted acupuncture effects in chronic pain patients; namely high temporal summation of pain (TS) indicating spinal synaptic facilitation as well as a low vibration detection threshold (VDT) indicating a loss of Aβ-fiber function. Pinprick induced TS and VDT were assessed by standardized, validated methods at the most painful body site and a pain free control site in 100 chronic pain patients receiving six acupuncture sessions as part of an interdisciplinary multimodal pain treatment (IMPT). Immediate change in pain intensity after the first acupuncture session (first treatment on the first day of IMPT) was assessed by the verbal rating scale (VRS, 0-100). After 4 weeks of treatment, patients indicated in a questionnaire whether acupuncture had relieved pain immediately and whether it had contributed to overall pain reduction and well-being after IMPT. Logistic regression analysis revealed an association between high TS at the control site and a reduction in pain intensity of at least 30% (VRS) after the first acupuncture (OR [95%-CI] 4.3 [1.6-11.8]). Questionnaire ratings of immediate pain relief after acupuncture were associated with high TS at the control site (OR [95%-CI] 3.8 [1.4-10.2] any pain relief, OR [95%-CI] 5.5 [1.7-17.1] over 50% pain reduction) and at the pain site (OR [95%-CI] 3.2 [1.2-8.9] any pain relief). Appraisals of the contribution of acupuncture to overall pain reduction and well-being after IMPT were not associated with TS. The VDT was not associated with any outcome. This explorative study provides first-time evidence that high TS, especially at a pain free control site, but not VDT, might predict immediate analgesic response to acupuncture in chronic pain patients. Thus, highly centrally sensitized chronic pain patients might respond particularly well to acupuncture.
Learn More >Increasing evidence for the efficacy of analgesic placebo effects in laboratory studies with healthy persons raises the question whether placebos could be used to improve the treatment of pain patients. Expectancies play a central role in shaping analgesic placebo but also nocebo effects.
Learn More >The emerging role of inflammation in the initiation and maintenance of neuropathic pain has been confirmed. Previous studies have reported that miR138 has neuroprotective and anti-inflammatory effects in animal models of spinal cord injury and in human coronary artery endothelial cell injury, while its effect on neuropathic pain is still not known. As the mechanism of neuropathic pain remains unclear, we investigated whether miR138 is involved in the development of neuropathic pain and the role of miR138 in the modulation of inflammation in the spinal cord in a mouse model of neuropathic pain induced by spared sciatic nerve injury (SNI).
Learn More >17β-estradiol plays a role in pain sensitivity, analgesic drug efficacy, and neuropathic pain prevalence, but the underlying mechanisms remain unclear. Here, we investigated whether voltage-gated chloride channel-3 (ClC-3) impacts the effects of 17β-estradiol (E2) on spared nerve injury (SNI)-induced neuropathic pain in ovariectomized (OVX) female Sprague Dawley rats that were divided into OVX, OVX + SNI, OVX + SNI + E2, OVX + SNI + E2 + DMSO (vehicle, dimethyl sulfoxide), or OVX + SNI + E2+Cltx (ClC-3-blocker chlorotoxin) groups. Changes in ClC-3 protein expression were monitored by western blot analysis. Behavioral testing used the paw withdrawal threshold to acetone irritation and paw withdrawal thermal latency (PWTL) to thermal stimulation. Immunofluorescence indicated the localization and protein expression levels of ClC-3. OVX + SNI + E2 rats were subcutaneously injected with 17β-estradiol once daily for 7 days; a sheathed tube was implanted, and chlorotoxin was injected for 4 days. Intrathecal Cltx to OVX and OVX + SNI rats was administered for 4 consecutive days (days 7-10 after SNI) to further determine the contribution of ClC-3 to neuropathic pain. Patch clamp technology in current clamp mode was used to measure the current threshold (rheobase) dorsal root ganglion (DRG) neurons and the minimal current that evoked action potentials (APs) as excitability parameters. The mean number of APs at double-strength rheobase verified neuronal excitability. There was no difference in behaviors and ClC-3 expression after OVX. Compared with OVX + SNI rats, OVX + SNI + E2 rats showed a lower paw withdrawal threshold to the acetone stimulus, but the PWTL was not significantly different, indicating increased sensitivity to cold but not to thermal pain. Co-immunofluorescent data revealed that ClC-3 was mainly distributed in A- and C-type nociceptive neurons, especially in medium/small-sized neurons. 17β-estradiol administration was associated with increased expression of ClC-3. 17β-estradiol-induced increase in ClC-3 expression was blocked by co-administration of Cltx. Cltx causes hyperalgesia and decreased expression of ClC-3 in OVX rats. Patch clamp results suggested that 17β-estradiol attenuated the excitability of neurons induced by SNI by up-regulating the expression of ClC-3 in the DRG of OVX rats. 17β-estradiol administration significantly improved cold allodynia thresholds in OVX rats with SNI. The mechanism for this decreased sensitivity may be related to the upregulation of ClC-3 expression in the DRG.
Learn More >Mechanisms of postherpetic neuralgia (PHN) are still not clear. Transcripts such as microRNA (miRNA) and circular RNA (circRNA) in the affected skin may take part in the initiation and development of this neuropathic pain; however, their expression profiles in skins of PHN patients have not been reported. The PHN affected skin and the mirror skin were collected and subjected to miRNA and circRNA microarray, and expression profiles were comparatively analyzed. There were 317 differently expressed miRNAs in PHN affected skin compared with mirror skin (fold change ≥2.0), and 13 of them showed fold change >10 in the PHN skin. Only one circRNA, hsa_circRNA_405463 showed fold change >2 in PHN skin, however, 31 circRNAs with fold change ≥1.5. To evaluate functions of differential miRNAs, their target mRNAs were predicted and bioinformatics analyses including gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway were conducted. Target mRNAs significantly (P<0.05) enriched in 85 pathways, such as FoxO, AMPK, MAPK and pathway. These data reported for the first time that miRNA and circRNA differentially expressed in the PHN skin and these transcripts with abnormal expression could be potential targets to treat PHN.
Learn More >Accumulating evidence from neuroimaging studies has supported that chronic pain could induce changes in brain function. However, few studies have focused on the dynamic regional homogeneity (dReHo) of trigeminal neuralgia (TN). In this study, twenty-eight TN patients and 28 healthy controls (HC) were included. Based on the resting-state fMRI (rsfMRI), we detected abnormalities in dReHo in the TN patients. Patients with TN had decreased dReHo in the left middle temporal gyrus, superior parietal lobule, and precentral gyrus, and increased dReHo in the thalamus. Furthermore, the increase in dReHo in the thalamus was positively correlated with duration of TN ( = 0.485, = 0.012). These results provide compelling evidence for abnormal resting-state brain activity in TN and suggest that the duration of TN may play a critical role in brain function.
Learn More >In the anesthetized cat the correlation between the ongoing cord dorsum potentials (CDPs) recorded from different lumbar spinal segments has a non-random structure, suggesting relatively stable patterns of functional connectivity between the dorsal horn neuronal ensembles involved in the generation of these potentials. During the nociception induced by the intradermic injection of capsaicin, the patterns of segmental correlation between the spontaneous CDPs acquire other non-random configurations that are temporarily reversed to their pre-capsaicin state by the systemic injection of lidocaine, a procedure known to decrease the manifestation of neuropathic pain in both animals and humans. We have now extended these studies and utilized machine learning for the automatic extraction and selection of particular classes of CDPs according to their shapes and amplitudes. By using a Markovian analysis, we disclosed the transitions between the different kinds of CDPs induced by capsaicin and lidocaine and constructed a global model based on the changes in the behavior of the CDPs generated along the whole set of lumbar segments. This allowed the identification of the different states of functional connectivity within the whole ensemble of dorsal horn neurones attained during nociception and their transitory reversal by systemic administration of lidocaine in preparations with the intact neuroaxis and after spinalization. The present observations provide additional information on the state of self-organized criticality that leads to the adaptive behavior of the dorsal horn neuronal networks during nociception and antinociception both shaped by supraspinal descending influences.
Learn More >In light of growing concerns about opioid analgesics, developing new non-pharmacologic pain control techniques has become a high priority. Adjunctive virtual reality can help reduce acute pain during painful medical procedures. However, for some especially painful medical procedures such as burn wound cleaning, clinical researchers recommend that more distracting versions of virtual reality are needed, to further amplify the potency of virtual reality analgesia. The current study with healthy volunteers explores for the first time whether interacting with virtual objects in Virtual Reality (VR) via "hands free" eye-tracking technology integrated into the VR helmet makes VR more effective/powerful than non-interactive/passive VR (no eye-tracking) for reducing pain during brief thermal pain stimuli.
Learn More >Nocebo effects encompass negative responses to inert interventions in the research setting and negative outcomes with active treatments in the clinical research or practice settings, including new or worsening symptoms and adverse events, stemming from patients' negative expectations and not the pharmacologic action of the treatment itself. Numerous personality, psychosocial, neurobiological, and contextual/environmental factors contribute to the development of nocebo effects, which can impair quality of life and reduce adherence to treatment. Biologics are effective agents widely used in autoimmune disease, but their high cost may limit access for patients. Biosimilar products have gained regulatory approval based on quality, safety, and efficacy comparable to that of originator biologics in rigorous study programs. In this review, we identified gaps in patients' and healthcare professionals' awareness, understanding, and perceptions of biosimilars that may result in negative expectations and nocebo effects, and may diminish their acceptance and clinical benefits. We also examined features of nocebo effects with biosimilar treatment that inform research and clinical practices. Namely, when biosimilars are introduced to patients as possible treatment options, we recommend adoption of nocebo-reducing strategies to avoid negative expectations, including delivery of balanced information on risk-benefit profiles, framing information to focus on positive attributes, and promoting shared decision-making processes along with patient empowerment. Healthcare professionals confident in their knowledge of biosimilars and aware of bias-inducing factors may help reduce the risk of nocebo effects and improve patients' adherence in proposing biosimilars as treatment for autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease.
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