The journal of pain : official journal of the American Pain Society
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The use of rodents in preclinical studies has contributed greatly to our understanding of the pathophysiology of chronic neuropathic pain. These animal models are limited because of their poor clinical translation. We developed a pig model for chronic pain caused by surgically induced peripheral neuritis trauma (PNT). Seventy-five percent of the animals exhibited mechanical and tactile allodynia, which are indicative of painful neuropathy, by day 28 after surgery. Importantly, the PNT-injured pigs retained their ability to walk or to stand on their injured leg. Messenger RNA analysis of acute inflammatory cytokines calcitonin gene-related peptide and brain-derived neurotrophic factor at the site of injury suggests transient inflammation followed by a persistent high level of neurologic markers. Gabapentin and morphine effectively inhibited hypersensitivity to von Frey filaments and to feather stimuli, and reversed spontaneous pain-related behavior in a dose-related manner. No analgesic effect was detected in PNT-injured pigs after treatment with aprepitant, similar to observations in humans and contrary to observations in rodents. In conclusion, PNT-induced trauma in pigs may comprise a valid preclinical model for the study of the chronification of peripheral nerve injury and for the study of new pain therapies. ⋯ This article presents the characterization of a new peripheral neuritis trauma (PNT) model in pigs. The pig PNT model could help close the translational gap between preclinical and clinical responses and may contribute to improved efficacy or safety of candidate drugs.
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Randomized Controlled Trial
Cognitive-behavioral based physical therapy for patients with chronic pain undergoing lumbar spine surgery: a randomized controlled trial.
The purpose of this study was to determine the efficacy of a cognitive-behavioral-based physical therapy (CBPT) program for improving outcomes in patients after lumbar spine surgery. A randomized controlled trial was conducted on 86 adults undergoing a laminectomy with or without arthrodesis for a lumbar degenerative condition. Patients were screened preoperatively for high fear of movement using the Tampa Scale for Kinesiophobia. Randomization to either CBPT or an education program occurred at 6 weeks after surgery. Assessments were completed pretreatment, posttreatment and at 3-month follow-up. The primary outcomes were pain and disability measured by the Brief Pain Inventory and Oswestry Disability Index. Secondary outcomes included general health (SF-12) and performance-based tests (5-Chair Stand, Timed Up and Go, 10-Meter Walk). Multivariable linear regression analyses found that CBPT participants had significantly greater decreases in pain and disability and increases in general health and physical performance compared with the education group at the 3-month follow-up. Results suggest a targeted CBPT program may result in significant and clinically meaningful improvement in postoperative outcomes. CBPT has the potential to be an evidence-based program that clinicians can recommend for patients at risk for poor recovery after spine surgery. ⋯ This study investigated a targeted cognitive-behavioral-based physical therapy program for patients after lumbar spine surgery. Findings lend support to the hypothesis that incorporating cognitive-behavioral strategies into postoperative physical therapy may address psychosocial risk factors and improve pain, disability, general health, and physical performance outcomes.
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In contrast to women with relatively asymptomatic endometriosis, women with endometriosis-associated chronic pelvic pain (CPP) exhibit nonpelvic hyperalgesia and decreased gray matter volume in key neural pain processing regions. Although these findings suggest central pain amplification in endometriosis-associated CPP, the underlying changes in brain chemistry and function associated with central pain amplification remain unknown. We performed proton spectroscopy and seed-based resting functional connectivity magnetic resonance imaging to determine whether women with endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions. Relative to age-matched pain-free controls, women with endometriosis-associated CPP displayed increased levels of combined glutamine-glutamate (Glx) within the anterior insula and greater anterior insula connectivity to the medial prefrontal cortex (mPFC). Increased connectivity between these regions was positively correlated with anterior insula Glx concentrations (r = .87), as well as clinical anxiety (r = .61, P = .02), depression (r = .60, P = .03), and pain intensity (r = .55, P = .05). There were no significant differences in insula metabolite levels or resting-state connectivity in endometriosis patients without CPP versus controls. We conclude that enhanced anterior insula glutamatergic neurotransmission and connectivity with the mPFC, key regions of the salience and default mode networks, may play a role in the pathophysiology of CPP independent of the presence of endometriosis. ⋯ Similar to other chronic pain conditions, endometriosis-associated pelvic pain is associated with altered brain chemistry and function in pain processing regions. These findings support central pain amplification as a mechanism of chronic pelvic pain, and clinicians should consider the use of adjunctive therapies that target central pain dysfunction in these women.
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Chronic back pain (CBP) is associated with circumscribed atrophy in gray matter (GM) predominantly localized in areas of the so-called pain matrix and the prefrontal cortex (PFC). Previous studies applying voxel-based morphometry (VBM) for identifying structural brain alterations related to CBP have reported inconsistent results, were limited to small sample sizes, and often did not control for medication. We therefore used VBM for high-resolution magnetic resonance images to investigate the association of CBP and regional GM volume in 111 individuals with CBP and 432 pain-free controls derived from the representative Study of Health in Pomerania, controlling for effects of medication. CBP was associated with decreased regional GM in the ventrolateral PFC and dorsolateral PFC, both the ventral and dorsal medial PFC, and the anterior insula. Pain intensity showed a weak negative correlation with GM volume in the left dorsolateral PFC, ventrolateral PFC, and anterior cingulate cortex. The CBP sample showed alterations in regions commonly associated with pain processing and emotional demands. To our knowledge, this is the first VBM study reporting decreased regional GM volume in the medial PFC in a CBP sample. We were unable to confirm alterations in regions other than the dorsolateral PFC and the insula. ⋯ Previous studies reported inconsistent results for brain areas altered in chronic pain conditions, which may be in part attributable to small sample sizes, medication use, or emotional comorbidities. This study in a large and representative cohort helps to clarify these issues.