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Breast carcinoma causes severe pain, which decreases the quality of life of patients. Current treatments produce adverse effects and have limited efficacy. Transient potential receptor ankyrin 1 (TRPA1) is related to the onset of cancer and neuropathic pain. The aim of this study was to evaluate the involvement of TRPA1 in a model of breast carcinoma. We injected 4T1 cells in the fourth caudal mammary fat pad of female BALB/c mice, and after 20 days we observed mechanical and cold allodynia and spontaneous nociception behavior (mouse grimace scale detection, MGS). TRPA1 selective antagonist (HC-030031 or A-967079) administration or intrathecal administration of TRPA1 antisense (AS) oligonucleotide was performed. The activity of NADPH oxidase, superoxide dismutase (SOD) and hydrogen peroxide (HO) levels were evaluated. The chemical hyperalgesia produced by a TRPA1 agonist (allyl isothiocyanate, AITC) was also detected. The administration of TRPA1 antagonists, TRPA1 AS, or antioxidant, transiently attenuated MGS, or mechanical and cold allodynia. Intraplantar injection of AITC also caused nociception. NADPH oxidase or SOD activity and HO levels were increased in the sciatic nerve and hind paw skin samples. The 4T1 cells did not express TRPA1, and the use of HC-030031 or α-lipoic acid did not reduce the cytotoxic effect of a chemotherapeutic drug (paclitaxel). Thus, TRPA1 could be investigated as a target for breast carcinoma pain treatment.
Learn More >Previous research suggests that multisensory body illusions that alter the conscious bodily experience can modulate pain in osteoarthritis, which may be a result of modifying cortical misrepresentations of the painful body part. However, the longevity and underlying mechanisms of such illusion-induced analgesia is unknown.
Learn More >To compare the effectiveness of deep tissue massage, supervised strengthening and stretching exercises, and a combined therapy (exercise followed by massage) (index groups), with advice to stay active (control group).
Learn More >Postoperative pain is not adequately managed in greater than 40% of surgical patients and is a high priority for perioperative research. In this meta-analysis, we examined studies comparing postoperative opioid consumption and pain scores in surgical patients who received methadone by any route versus those who received another opioid by any route. Studies were identified from PubMed, Cochrane, Web of Science, EMBASE, and Scopus from January 1966-November 2018. Pooled odds ratios were calculated for a primary outcome of postoperative opioid consumption and secondary outcomes of time-to-extubation, time-to-first postoperative analgesia request, satisfaction, hospital length-of-stay, and complications. Postoperative pain scores were assessed qualitatively. Ten studies (617 patients) were included. Postoperative opioid consumption at 24 hours was lower in the methadone group versus control (MD = -15.22 mg oral morphine equivalents, 95% CI -27.05 to -3.38; P=.01). Patients in the methadone group generally reported lower postoperative pain scores in seven of ten studies. Meta-analysis revealed greater satisfaction scores with analgesia in the methadone group versus control (0-100 visual analog scale; MD = 7.16, 95% CI 2.30 to 12.01; P=.004). There was no difference in time-to-extubation, time-to-first analgesia request, hospital length of stay, or complications (nausea, sedation, respiratory depression, hypoxemia). The results demonstrate that surgical patients who received intraoperative methadone had lower postoperative opioid consumption, generally reported lower pain scores, and experienced better satisfaction with analgesia. However, these advantages need to be weighed carefully against dangerous risks with perioperative methadone, specifically respiratory depression and arrhythmia. Future studies should explore logistics, safety, and cost-effectiveness.
Learn More >Clinical hypnosis for pain management cultivates specific skills to enhance general self-regulation and address pain. Hypnosis is well suited to integrative medicine settings; however, questions persist about its feasibility. This article describes a financially viable hypnosis practice model implemented in an integrative medicine clinic, providing initial feasibility data about rates of referral, participation, reimbursement, and provider retention. The specific processes required to establish and implement hypnosis services were detailed, including instruction in billing, reimbursement data, and a training model to enhance reach of services. Insurer reimbursement data and operational costs were examined from three hypnosis groups conducted between September 2017 and March 2018. Furthermore, information on referral patterns and enrollment in treatment was collected from program initiation in September 2017 to January 2019. Provider retention in training with the expansion of supervision in the program's second year was also examined. Of 258 individuals referred to hypnosis, 124 (48%) enrolled in group treatment. Analysis of insurer reimbursement over a subset of enrollees from three completed groups ( = 26) indicated an average collection of $95.85 per patient per session, equating to $706.86 per patient for the eight-session treatment. This extrapolates to $4,926.82 in total per seven-person group for the entirety of the eight-session treatment. After an annual training workshop, provider retention significantly increased (to 81% of eligible trained providers) with the initiation of twice-monthly clinical supervision focusing on transitioning from training to practice. This analysis indicates that a training- and practice-based research model of clinical hypnosis is feasible and financially sustainable in an integrative medicine setting.
Learn More >Older adults experience significant chronic pain after hip fracture, resulting in decreased physical functioning. However, pain investigation in this population is mostly limited to self-reported pain intensity. Detailed pain assessment may identify intervention targets other than pain relief. The aim of this study is to investigate multiple dimensions of pain experience (intensity, sensory, affective, evaluative and miscellaneous dimensions) and to correlate them to lower limb functionality and limitations in daily living activities.
Learn More >Pain is one of the most frequent nonmotor impairments in Parkinson's disease (PD) and is hypothesized to be associated with altered nociceptive pain processing. Our aims were to investigate differences in widespread pressure pain sensitivity between PD patients with and without pain and healthy controls and to assess the relationship of health-related quality of life and sleep quality with pressure pain sensitivity.
Learn More >To evaluate the human abuse potential, pharmacokinetics, pharmacodynamics, and safety of oral NKTR-181 (oxycodegol), a novel full mu-opioid receptor agonist, relative to oral oxycodone.
Learn More >The aminosteroid U73122 is frequently used as a phospholipase C (PLC) inhibitor and as such was used to investigate PLC-dependent activation and modulation of the transient receptor potential ankyrin type 1 (TRPA1) receptor channel. However, U73122 was recently shown to activate recombinant TRPA1 directly, albeit this interaction was not further explored. Our aim was to perform a detailed characterization of this agonistic action of U73122 on TRPA1. We used Fura-2 calcium microfluorimetry and the patch clamp technique to investigate the effect of U73122 on human and mouse wild type and mutant (C621S/C641S/C665S) TRPA1 expressed in HEK293t cells, as well as native TRPA1 in primary afferent neurons from wild type and TRPV1 and TRPA1 null mutant mice. In addition, we measured calcitonin gene-related peptide (CGRP) release from skin isolated from wild-type and TRPA1 null mutant mice. Human and mouse TRPA1 channels were activated by U73122 in the low nanomolar range. This activation was only partially dependent upon modification of the N-terminal cysteines 621, 641, and 665. U73122 also activated a subpopulation of neurons from wild-type and TRPV1 null mutant mice, but this effect was absent in mice deficient of TRPA1. In addition, U73122 evoked marked calcitonin gene-related peptide (CGRP) release from skin preparations of wild type but not TRPA1 null mutant mice. Our results indicate that U73122 is a potent and selective TRPA1 agonist. This effect should be taken into account when U73122 is used to inhibit PLC in TRPA1-expressing cells, such as primary nociceptors. In addition, U73122 may present a novel lead compound for the development of TRPA1-targeting drugs.
Learn More >Effectively treating chronic pain remains a therapeutic challenge in the clinic. Recent evidence has shown the inhibition of the soluble epoxide hydrolase (sEH) to be an effective strategy to limit chronic pain in preclinical models, horses and companion animals. Determining the safety ofsEH inhibition in addition to this demonstrated efficacy is a critical step to the further development ofsEH inhibitors (sEHI) as analgesics. Here we describe a comparison of thesEHI TPPU with other first in class analgesics for human chronic pain. We assess the development of tolerance to the analgesia mediated by TPPU with extended use. We also assess for CNS effects by measuring changes in motor control and functioning. ThesEHI are multimodal analgesics that have demonstrated potent efficacy against chronic pain. They have previously been tested and show no reward potential using operant methods. The results of the current experiments show that they lack motor function effects and also lack the development of tolerance with extended dosing.
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