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Cellulite is a skin condition that significantly affects women, characterized by “holes” or depressions in the skin, affecting approximately 95% of women at some point in their lives. Cellulite often presents inflammatory symptoms such as increased skin temperature and hyperalgesia. Photobiomodulation, whether applied locally or systemically, has demonstrated important anti-inflammatory effects in various conditions. This study investigates the effects of local and systemic photobiomodulation on hip culottes temperature increases and hyperalgesia in patients with grades 2 to 4 cellulite. Cellulite assessment was carried out using detailed anamnesis, photographic records, algometry, and infrared thermography. Participants received randomized bilateral treatment with or without systemic irradiation using LED photobiomodulation on the hip culottes for four weeks, three times a week. This study aimed to evaluate the effect of photobiomodulation, especially locally applied, together or not with systemic irradiation, on cellulite hyperalgesia and skin temperature among 25 female participants. The group that received only LED treatment showed an increase in pain threshold of 8% and 20% on the right and left sides, respectively, while the group treated with LED + ILIB showed an increase in pain threshold of 32% on both sides. Local photobiomodulation produced a skin temperature decrease of 0.4 °C, while the combination of local and systemic irradiation produced an average skin temperature decrease of 1.2 °C. Our results clearly demonstrate a significantly beneficial effect of LED therapy for cellulite treatment, especially when administered in combination with mILIB, leading to a significant reduction of pain hypersensitivity and skin temperature, indicating a regional subcutaneous improvement of the inflammatory status.

Background: Peripheral neuromodulation is often used as chronic neuropathic pain treatment. Percutaneous electrical nerve stimulation (PENS) is generally utilized with several probes at the same time and repeated treatments. Objectives: Evaluate the short- and long-term efficacy of a single probe and single shot PENS approach. Study Design: Multicenter, prospective, observational study. Setting: Four Italian pain therapy centers. Methods: Inclusion criteria were age ≥ 18 and ≤ 80 years, presence of severe peripheral neuropathic pain lasting more than 3 months, localized and refractory to pharmacological therapies. Patients with infection, coagulopathies, psychiatric disorders, pacemakers, or implantable cardiac defibrillators were excluded. Patients: Seventy-six patients (47 women, 29 men), mean age 62 ± 14 years, affected by neuralgia (21 herpes zoster infection, 31 causalgia, 24 postoperative pain) were enrolled in the study. Intervention: After localization of trigger point and/or allodynic/hyperalgesic area, PENS therapy was achieved with a single 21 gauge conductive probe tunneled percutaneously and a neurostimulator device. Measurement: Numerical Rating Scale (NRS) and Neuropathic Pain Scale (NPS) were assessed at baseline, 60 minutes after PENS, at one week, after one, 3, and 6 months; perceived health outcome was measured with Euroqol-5 dimension (EQ-5D) questionnaire at baseline and at 6 months. Adverse events and patient satisfaction were reported. Results: NRS and NPS decreased significantly after 60 minutes and the reduction remained constant over time at follow-up. EQ-5D increased significantly with respect to the baseline. Two nonclinically significant adverse events (one contralateral dysestesia and one self-resolving hematoma) were observed. Limitations: Small sample size and non-randomized observational study; high prevalence of post-herpetic and occipital neuralgias. Conclusion: PENS therapy produced significant and long-lasting pain relief in chronic peripheral neuropathic pains of different etiology. The present study confirms the feasibility, safety, and repeatability of this minimally invasive technique. Key words: Neuropathic pain, neuromodulator, peripheral nerve, percutaneous stimulation

The TRPM8 channel, a temperature-sensitive ion channel, plays a crucial role in various physiological processes, particularly in the modulation of inflammation and nociception. Although electroacupuncture (EA) is a recognized analgesic treatment for pain conditions, its interaction with TRPM8 remains underexplored. This study aims to determine TRPM8's role in EA-induced analgesia using a murine model of inflammatory pain. Mechanical allodynia, evidenced by a reduced paw withdrawal threshold (PWT), was induced in both wild-type and mice through CFA injection. EA applied at the GB34 and LR3 acupoints significantly alleviated mechanical allodynia in both groups. In wild-type mice, the analgesic effects of EA were partially reversed by naloxone (an opioid receptor antagonist) or AM251 (a CB1 receptor antagonist) and fully reversed by their combination. In contrast, only AM251 reversed EA-induced analgesia in or TRPM8-inhibited wild-type mice (via AMTB treatment, a TRPM8 antagonist), indicating no involvement of the opioid pathway. Additionally, the combination of menthol, a partial TRPM8 agonist, and EA enhanced analgesia in wild-type mice. In or AMTB-pretreated mice, the CB1 receptor agonist WIN 55,212-2 (WIN) exhibited stronger analgesic effects compared to wild-type controls. These findings suggest that EA at LR3 and GB34 mediates analgesia through both opioid and endocannabinoid pathways. TRPM8 is critical for EA to activate the opioid pathway, while its inhibition or deletion shifts the analgesic mechanism towards reliance on the cannabinoid system. Understanding this mechanistic shift may help optimize EA treatment strategies and improve pain management outcomes.

Abstract Objective. To compare the short-term effects of manual therapy and exercise on pain, related disability, range of motion, and pressure pain thresholds between subjects with mechanical neck pain and whiplash-associated disorders. Methods. Twenty-two subjects with mechanical neck pain and 28 with whiplash-associated disorders participated. Clinical and physical outcomes including neck pain intensity, neck-related disability, and pain area, as well as cervical range of motion and pressure pain thresholds over the upper trapezius and tibialis anterior muscles, were obtained at baseline and after the intervention by a blinded assessor. Each subject received six sessions of manual therapy and specific neck exercises. Mixed-model repeated measures analyses of covariance (ANCOVAs) were used for the analyses. Results. Subjects with whiplash-associated disorders exhibited higher neck-related disability (P = 0.021), larger pain area (P = 0.003), and lower pressure pain thresholds in the tibialis anterior muscle (P = 0.009) than those with mechanical neck pain. The adjusted ANCOVA revealed no between-group differences for any outcome (all P > 0.15). A significant main effect of time was demonstrated for clinical outcomes and cervical range of motion with both groups experiencing similar improvements (all P < 0.01). No changes in pressure pain thresholds were observed in either group after treatment (P > 0.222). Conclusions. The current clinical trial found that subjects with mechanical neck pain and whiplash-associated disorders exhibited similar clinical and neurophysiological responses after a multimodal physical therapy intervention, suggesting that although greater signs of central sensitization are present in subjects with whiplash-associated disorders, this does not alter the response in the short term to manual therapy and exercises.

Electroacupuncture (EA) effectively improves arthritis-induced hyperalgesia and allodynia by repressing spinal microglial activation, which plays a crucial role in pain hypersensitivity following tissue inflammation. However, the mechanism by which EA suppresses spinal microglial activation in monoarthritis (MA) remains unclear. In the present study, a rat model of MA was established through unilateral ankle intra-articular injection of complete Freund’s adjuvant (CFA). The relationship among P2Y12 receptor (P2Y12R) expression, spinal microglial activation, and EA analgesia was investigated using quantitative real-time PCR (qRT‒PCR), western blotting, immunofluorescence (IF), and behavioral testing. The results found that EA treatment at the ipsilateral “Huantiao” (GB30) and “Yanglingquan” (GB34) acupoints markedly attenuated pain and spinal microglia M1 polarization in MA rats. In particular, P2Y12R expression was significantly increased at the mRNA and protein levels in the spinal dorsal horn in MA rats, whereas EA treatment effectively repressed the MA-induced upregulation of P2Y12R. IF analysis further revealed that most P2Y12R was expressed in microglia in the spinal dorsal horn. Pharmacological inhibition of P2Y12R by its antagonist (AR-C69931MX) decreased MA-induced spinal microglial activation and subsequent proinflammatory cytokine production. Consequently, AR-C69931MX significantly intensified the anti-pain hypersensitive function of EA in MA rats. Taken together, these results demonstrate that EA alleviates MA-induced pain by suppressing P2Y12R-dependent microglial activation.

Opioid-induced hyperalgesia (OIH) is a condition in which prolonged opioid use paradoxically increases sensitivity to noxious stimuli, resulting in heightened discomfort and diminished tolerance. This study aimed to investigate the clinical effects of Memantine in managing OIH symptoms in opioid-dependent patients. A randomized clinical trial involving 36 opioid-addicted patients diagnosed with opioid-induced hyperalgesia (OIH) was conducted between January and June 2022. Participants were randomly assigned to one of two groups: an intervention group receiving 10 mg/day of memantine, and a control group receiving placebo. The Cold Pressure Test (CPT) and Visual Analog Scale (VAS) were utilized to assess pain tolerance and intensity, respectively. The memantine group showed significantly increased cold pain tolerance at two and four weeks post-intervention ( p  = 0.005 and p  < 0.001) and a significant reduction in pain intensity at two week ( p  = 0.001), though not at four weeks ( p  = 0.4536). Repeated measures ANOVA indicated significant within-subject effects of time for both CPT (F = 41.694, p  = 0.001, η² = 0.558) and VAS (F = 69.065, p  = 0.001, η² = 0.677), while between-group and interaction effects were not significant. This study offers preliminary support for the potential efficacy of 10 mg/day memantine in alleviating OIH symptoms, warranting further investigation to confirm these findings. Trial registration IRCT registration number IRCT20211112053045N1. Registration date 07/12/2021. IRCT URL https//irct.behdasht.gov.ir/trial/60,058. Ethical code IR.ZUMS.REC.1400.26.

High-dose remifentanil during surgery paradoxically increases postoperative pain intensity and morphine consumption. Cyclooxygenase inhibitors decrease prostaglandin synthesis, thereby antagonizing N-methyl-d-aspartate receptor activation, and may reduce hyperalgesia. This study was performed to evaluate whether postoperative morphine consumption increased following intraoperative continuous remifentanil infusion and whether this could be prevented by intravenous ibuprofen pretreatment. A randomized controlled study. Single university hospital, study period from September 2014 to March 2015. One hundred and twenty patients undergoing pancreaticoduodenectomy. After induction of anesthesia, patients received remifentanil target-controlled infusion (effect site concentration of 4 ng/mL or 1 ng/mL) with or without intravenous ibuprofen (800 mg). Postoperative cumulative total morphine consumption and pain intensity were assessed. Intraoperative remifentanil use in patients receiving high-dose remifentanil was more than 3-fold higher than that in patients receiving low-dose remifentanil (2666.8 ± 858.4 vs 872.0 ± 233.3 μg, respectively; P< .001). However, cumulative total morphine consumption at postoperative 1, 3, 6, 12, 24, and 48 hours did not differ among the groups. There were no differences among the groups in the self-administered analgesic dose by the patients using a controlled analgesia device, number of self-administration attempts, numerical rating scale for pain, or analgesic side effects. We found no influence on postoperative pain after high-dose remifentanil in patients undergoing pancreaticoduodenectomy. Addition of intravenous ibuprofen did not reduce postoperative morphine consumption or pain intensity. •High-dose remifentanil increases postoperative pain intensity and morphine consumption.•Ibuprofen decreases prostaglandin synthesis and may reduce hyperalgesia.•We found no influence on postoperative pain after high-dose remifentanil infusion.•Intravenous ibuprofen did not reduce morphine consumption or pain intensity.

As chronic pain affects 115 million people and costs $600B annually in the US alone, effective noninvasive nonpharmacological remedies are desirable. The purpose of this study was to determine the efficacy and the generalisability of Noxipoint therapy (NT), a novel electrotherapy characterised by site-specific stimulation, intensity-and-submodality-specific settings and a immobilization period, for chronic neck and shoulder pain. Ninety-seven heavily pretreated severe chronic neck/shoulder pain patients were recruited; 34 and 44 patients were randomly allocated to different treatment arms in two patient-and-assessor-blinded, randomised controlled studies. The participants received NT or conventional physical therapy including transcutaneous electrical nerve stimulation (PT-TENS) for three to six 90-minute sessions. In Study One, NT improved chronic pain (−89.6%, Brief Pain Inventory, p < 0.0001, 95% confidence interval), function (+77.4%, range of motion) and quality of life (+88.1%) at follow-up (from 4 weeks to 5 months), whereas PT-TENS resulted in no significant changes in these parameters. Study Two demonstrated similar advantages of NT over PT-TENS and the generalisability of NT. NT-like treatments in a randomised rat study showed a similar reduction in chronic hypersensitivity (−81%, p < 0.01) compared with sham treatments. NT substantially reduces chronic neck and shoulder pain, restores function and improves quality of life in a sustained manner.

The aim of this investigation was to evaluate the effects of local anaesthesia on nerve growth factor (NGF) induced masseter hyperalgesia. Healthy participants randomly received an injection into the right masseter muscle of either isotonic saline (IS) given as a single injection (n = 15) or an injection of NGF (n = 30) followed by a second injection of lidocaine (NGF + lidocaine; n = 15) or IS (NGF + IS; n = 15) in the same muscle 48 h later. Mechanical sensitivity scores of the right and left masseter, referred sensations and jaw pain intensity and jaw function were assessed at baseline, 48 h after the first injection, 5 min after the second injection and 72 h after the first injection. NGF caused significant jaw pain evoked by chewing at 48 and 72 h after the first injection when compared to the IS group, but without significant differences between the NGF + lidocaine and NGF + IS groups. However, the mechanical sensitivity of the right masseter 5 min after the second injection in the NGF + lidocaine group was significantly lower than the second injection in the NGF + IS and was similar to the IS group. There were no significant differences for the referred sensations. Local anaesthetics may provide relevant information regarding the contribution of peripheral mechanisms in the maintenance of persistent musculoskeletal pain.