The journal of pain : official journal of the American Pain Society
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Inflammatory cytokines contribute to lumbar radiculopathy. Regulation of cytokines for transient cervical injuries, with or without longer-lasting inflammation, remains to be defined. The C7 root in the rat underwent compression (10gf), chromic gut suture exposure (chr), or their combination (10gf+chr). Ipsilateral C7 spinal cord and dorsal root ganglia (DRG) were harvested at 1 hour after injury for real-time PCR analysis of IL-1beta, IL-6, and TNF-alpha. Cytokine mRNA increased after all 3 injuries. TNF-alpha mRNA in the DRG was significantly increased over sham after 10gf+chr (P = .026). Spinal IL-1beta was significantly increased over sham after 10gf and 10gf+chr (P < .024); IL-6 was significantly increased after 10gf+chr (P < .024). In separate studies, the soluble TNF-alpha receptor was administered at injury and again at 6 hours in all injury paradigms. Allodynia was assessed and tissue samples were harvested for cytokine PCR. Allodynia significantly decreased with receptor administration for 10gf and 10gf+chr (P < .005). Treatment also significantly decreased IL-1beta and TNF-alpha mRNA in the DRG for 10gf+chr (P < .028) at day 1. Results indicate an acute, robust cytokine response in cervical nerve root injury with varying patterns, dependent on injury type, and that early increases in TNF-alpha mRNA in the DRG may drive pain-related signaling for transient cervical injuries. ⋯ Inflammatory cytokine mRNA in the DRG and spinal cord are defined after painful cervical nerve root injury. Studies describe a role for TNF-alpha in mediating behavioral sensitivity and inflammatory cytokines in transient painful radiculopathy. Results outline an early response of inflammatory cytokine upregulation in cervical pain.
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Randomized Controlled Trial Comparative Study
Effect of morphine and pregabalin compared with diphenhydramine hydrochloride and placebo on hyperalgesia and allodynia induced by intradermal capsaicin in healthy male subjects.
Intradermal (ID) capsaicin injection in humans induces spontaneous pain, flare, primary hyperalgesia, secondary hyperalgesia, and allodynia. Secondary hyperalgesia and allodynia are a reflection of central sensitization. The effect of treatment of single doses of (1) pregabalin, 300 mg single oral dose, and (2) morphine, 10 mg IV, on the area of secondary hyperalgesia induced by ID capsaicin injection was studied by using a randomized, double-blinded, placebo-controlled, 4-period, cross-over design in 20 healthy men. Compared with active placebo diphenhydramine (50 mg oral dose), pregabalin and morphine significantly reduced the area of secondary hyperalgesia over 15 to 240 minutes after capsaicin injection (approximately 25%, P = .002 and approximately 33%, P < .001, respectively). A smaller reduction was observed when pregabalin and morphine were compared with true placebo (approximately 13%, P = .081 and approximately 24%, P = .009, respectively). Diphenhydramine, on the other hand, increased the area of secondary hyperalgesia in comparison with true placebo (approximately 16%, P = .061). The relationship between the baseline area of hyperalgesia and assay sensitivity suggests that establishing minimum entry criteria for the baseline area of hyperalgesia requirement increases the sensitivity of the assay. ⋯ These results suggest that the minimally invasive intradermal capsaicin model, when it is compared with true placebo, can potentially be used for an early assessment of relevant pharmacology of novel analgesic compounds in healthy subjects. This platform may provide a means to rapidly assess new analgesics and enhance dose selection and decision-making during clinical development.
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Randomized Controlled Trial
Reduction of pain-related fear and disability in post-traumatic neck pain: a replicated single-case experimental study of exposure in vivo.
For patients with acute post-traumatic neck pain (PTNP), pain-related fear has been identified as a potential predictor of chronic disability. If such is the case, fear reduction should enhance the prevention of further pain disability and distress after traumatic neck pain disability. However, exposure-based treatments have not been tested in patients with PTNP. Using a replicated single-case crossover phase design with multiple measurements, this study examined whether the validity of a graded exposure in vivo, as compared with usual graded activity, extends to PTNP. Eight patients who reported substantial pain-related fear were included in the study. Daily changes in pain intensity, pain-related fear, pain catastrophizing, and activity goal achievement were assessed. Before and after each intervention, and at 6-month follow-up, standardized questionnaires of pain-related fear and pain disability were administered, and, to quantify daily physical activity level, patients carried an ambulatory activity monitor. The results showed decreasing levels of self-reported pain-related fear, pain intensity, disability, and improvements in physical activity level only when graded exposure in vivo was introduced, and not in the graded activity condition. The results are discussed in the context of the search for customized treatments for PTNP. ⋯ This is the first study showing that the effects of graded exposure in vivo generalize to patients with chronic PTNP reporting elevated levels of pain-related fear. This could help clinicians to customize treatments for PTNP.
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The firing rate of low threshold motor units is decreased in constant force contractions during experimental pain. However, as firing rate is a determinant of force, it is unclear how force is maintained. Increased synergist muscle activity may compensate. This was investigated by evaluation of motor unit firing rate in synergist ankle plantar flexor muscles (triceps surae). Single motor unit action potentials were recorded in medial gastrocnemius and soleus muscles with fine wire electrodes in 10 subjects. Gross muscle activity was estimated from surface electromyographic (EMG) recordings. Bolus injections of 5% hypertonic saline were injected into lateral gastrocnemius to induce pain (low intensity, 0.5 mL; high intensity, 1.5 mL). Subjects gently plantar-flexed the ankle to recruit 1 to 4 motor units and performed 3 20-second contractions to this target before, during, and after pain. Firing rate decreased approximately 12% in synergist heads of triceps surae during pain and recovered after pain. Despite reduced firing rate, root-mean-square surface EMG amplitude did not change. The effect of nociceptor stimulation is not restricted to painful muscles but reduces motor unit firing in synergist muscles. Changes in synergist muscles cannot explain the maintenance of muscle force. Maintenance of surface EMG amplitude suggests recruitment of additional motor units. ⋯ This study showed that activity of synergist muscles can be affected by muscle pain. However, the changes in activity of synergist muscles may not compensate for changes in the painful muscle. This finding provides evidence of more widespread effects of pain on muscle control.
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We sought to examine whether the presence of a noncancer pain condition is independently associated with an increased risk for suicidal ideation, plan, or attempt after adjusting for sociodemographic and psychiatric risk factors for suicide and whether risk differs by specific type of pain. We analyzed data from the National Comorbidity Survey Replication, a household survey of U.S. civilian adults age 18 years and older (n = 5692 respondents). Pain conditions, nonpain medical conditions, and suicidal history were obtained by self-report. DSM-IV mood, anxiety, and substance use disorders were assessed using the World Health Organization's Composite International Diagnostic Interview. Antisocial and borderline personality traits were assessed with the International Personality Disorder Examination screening questionnaire. In unadjusted logistic regression analyses, the presence of any pain condition was associated with lifetime and 12-month suicidal ideation, plan, and attempt. After controlling for demographic, medical, and mental health covariates, the presence of any pain condition remained significantly associated with lifetime suicidal ideation (odds ratio, 1.4; 95% confidence interval, 1.1-1.8) and plan. Among pain subtypes, severe or frequent headaches and "other" chronic pain remained significantly associated with lifetime suicidal ideation and plan; "other" chronic pain was also associated with attempt. ⋯ The risk for suicidal thoughts and behaviors that may accompany back, neck, and joint pain can be accounted for by comorbid mental health disorders. There may be additional risk accompanying frequent headaches and "other" chronic pain that is secondary to psychosocial processes not captured by the mental disorders assessed.