Pain
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Anti-nerve growth factor (anti-NGF) treatment is analgesic in chronic inflammatory pain conditions without reducing inflammation. Hypothesizing that ongoing pain induced by inflammatory mediators is increased by long term sensitization of nociceptors, we combined the non-inflammatory NGF-sensitization model with an inflammatory ultraviolet-B (UV-B) model in human volunteers. UV-B irradiation of the skin presensitized with NGF 3 weeks before intensified the pre-existing NGF hyperalgesia during the inflammatory phase of UV-B and caused spontaneous pain in about 70% of the subjects. ⋯ Hyperalgesia and spontaneous pain coexisted in NGF/UV-B treated skin but did not significantly correlate (r < -0.1 at day 1 and r < 0.2 at day 3). We conclude that NGF can sensitize nociceptive endings such that inflammatory mediators may cause sufficient excitation to provoke spontaneous pain. Our results suggest that neuronal sensitization and level of inflammation represent independent therapeutic targets in chronic inflammatory pain conditions.
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Despite a high prevalence of pain and ongoing effort to understand and reduce pain, studies show that there remains a considerable unmet need for pain relief and management. In part, this may be due to patient's not adhering to treatment recommendations. ⋯ Randomized, controlled trials of brief communication skills training have shown improved outcomes in primary care settings for patients with fibromyalgia and acute pain. Thus, although treatment of chronic pain is challenging, good communication between health providers and patients can promote adherence and improve outcomes.
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Randomized Controlled Trial
Emotional modulation of pain and spinal nociception in persons with major depressive disorder (MDD).
Major depressive disorder (MDD) is associated with risk for chronic pain, but the mechanisms contributing to the MDD and pain relationship are unclear. To examine whether disrupted emotional modulation of pain might contribute, this study assessed emotional processing and emotional modulation of pain in healthy controls and unmedicated persons with MDD (14 MDD, 14 controls). Emotionally charged pictures (erotica, neutral, mutilation) were presented in 4 blocks. ⋯ Furthermore, emotional modulation of pain was observed in controls but not MDD, even though there were no group differences in NFR threshold or emotional modulation of NFR. Together, these results suggest supraspinal processes associated with emotion processing and emotional modulation of pain may be disrupted in MDD, but brain to spinal cord processes that modulate spinal nociception are intact. Thus, emotional modulation of pain deficits may be a phenotypic marker for future pain risk in MDD.
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Treating bone cancer pain poses a major clinical challenge, and the mechanisms underlying bone cancer pain remain elusive. EphrinB-EphB receptor signaling may contribute to bone cancer pain through N-methyl-d-aspartate receptor neuronal mechanisms. Here, we report that ephrinB-EphB signaling may also act through a Toll-like receptor 4 (TLR4)-glial cell mechanism in the spinal cord. ⋯ Intrathecal administration of an exogenous EphB1 receptor activator, ephrinB2-Fc, increased the expression of TLR4 and the levels of IL-1β and TNF-α, activated astrocytes and microglial cells, and induced thermal hypersensitivity. These ephrinB2-Fc-induced alterations were suppressed by spinal knockdown of TLR4. This study suggests that TLR4 may be a potential target for preventing or reversing bone cancer pain and other similar painful processes mediated by ephrinB-EphB receptor signaling.
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Chronic musculoskeletal pain can strain marriages, perhaps even to the point of engendering spouse criticism and hostility directed toward patients. Such negative spouse responses may have detrimental effects on patient well-being. While results of cross-sectional studies support this notion, we extended these efforts by introducing expressed emotion (EE) and interpersonal theoretical perspectives, and by using electronic diary methods to capture both patient and spouse reports in a prospective design. ⋯ Concurrent and lagged within-couple associations between patient's perceptions of spouse criticism/hostility and patient self-reported pain and spouses' observations of patient pain behaviors revealed that (1) patient perceived spouse criticism and hostility were correlated significantly with pain intensity, and spouse observed patient pain behavior was related significantly with patient perceived hostility at the same time point; (2) patient perceived spouse hostility significantly predicted patient pain intensity 3 hours later, and spouse observed pain behaviors significantly predicted patient perceived spouse hostility 3 hours later. Results support both EE and interpersonal models, and imply that a comprehensive model would combine these conceptualizations to fully illustrate how spouse criticism/hostility and patient pain interact to produce a negative spiral. Given that marital interactions are amenable to clinical intervention, improved insight into how spouse behavior and patient pain are tightly linked will encourage productive translational efforts to target this neglected area.