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As a protective mechanism, the cornea is sensitive to noxious stimuli. Here, we show that in mice, a high proportion of corneal TRPM8 cold-sensing fibers express the heat-sensitive TRPV1 channel. Despite its insensitivity to cold, TRPV1 enhances membrane potential changes and electrical firing of TRPM8 neurons in response to cold stimulation. This elevated neuronal excitability leads to augmented ocular cold nociception in mice. In a model of dry eye disease, the expression of TRPV1 in TRPM8 cold-sensing fibers is increased, and results in severe cold allodynia. Overexpression of TRPV1 in TRPM8 sensory neurons leads to cold allodynia in both corneal and non-corneal tissues without affecting their thermal sensitivity. TRPV1-dependent neuronal sensitization facilitates the release of the neuropeptide substance P from TRPM8 cold-sensing neurons to signal nociception in response to cold. Our study identifies a mechanism underlying corneal cold nociception and suggests a potential target for the treatment of ocular pain.
Learn More >Previous studies have indicated a positive relationship between self-compassion and psychological and emotional well-being in chronic pain populations. However, evidence on the role and mechanisms of self-compassion in pain perception is largely limited. The current study was designed to investigate the effects and a potential mechanism of self-compassion on experimental pain. Thirty healthy participants underwent a compassionate self-talk protocol, which was followed by cold pain exposure during which high-frequency heart rate variability (HF-HRV) was evaluated. The compassionate self-talk protocol successfully generated compassionate statements among the participants. Our behavioral data showed lower pain ratings in the self-compassion compared to the control condition. Moreover, self-compassion manipulation resulted in higher HF-HRV during pain, which was associated with lower pain ratings. We present interesting findings that a short period of compassionate self-talk may decrease experimental pain as well as mechanistic evidence surrounding bodily control over pain-related arousal indicated by HF-HRV. PERSPECTIVE: This study presents the first line of evidence that a short period of compassionate self-talk may be sufficient to reduce experimental pain. We also demonstrate increased bodily control as a potential mechanism underlying this effect.
Learn More >Chronic pain is a common symptom in rheumatic diseases, and the patient with pain and no signs of inflammation poses a challenge to the physician. Notably, all rheumatic diseases have components of non-inflammatory pain and a higher prevalence of fibromyalgia compared to the overall population. Hypothetically, a chronic pain stimulus may have stronger impact in a chronic inflammatory state, and the process towards a pain condition may be influenced by individual predisposition for development of chronic pain. In addition, the features of peripheral and central pain processing may be exacerbated by inflammation, and disturbed pain processing may be a feature contributing to widespread pain. We herein review and describe the prevalence of chronic pain and different pain modalities in the most common rheumatic diseases. In addition, the background mechanisms of non-inflammatory pain in rheumatic diseases are discussed. Finally, we here review the current strategies for pain management, with a special focus on non-inflammatory pain. The key message is that pain management should be individualized and based on a thorough pain analysis with investigation of the pain modality, localization and pain intensity. Other factors to consider are the underlying rheumatic disease and treatment, the patient's mental and physical health status and psychological factors.
Learn More >To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes).
Learn More >Fibromyalgia is a chronic pain syndrome characterized by central sensitization. A novel protocol based on slowly repeated evoked pain (SREP) appears to be a useful marker of pain sensitization in fibromyalgia patients. Whether SREP enhances diagnostic accuracy beyond key clinical symptoms that characterize fibromyalgia has not been examined.
Learn More >Compressive neuropathy is a recurring and challenging disease for patients, regardless of medical or surgical treatment. Neuropathological severity is associated with the force of mechanical compression. Available animal models do not address mechanical issues with reproducible outcomes. We used a chronic constriction injury model to analyze tension-controlled compressive neuropathy and achieve reproducible functional outcomes.
Learn More >The use of long-term opioid therapy for chronic pain remains common, yet data on long-term outcomes, especially after dose escalation, are sparse. This study examined potential benefits and harms associated with prescription opioid dose escalation. Participants from two institutions were enrolled in a two-year prospective cohort study. All participants (n=517) had a musculoskeletal pain diagnosis and were receiving a stable dose of long-term opioid therapy at baseline. Participants completed self-report measures of pain, disability, depression, and potential adverse effects at baseline and every six months for two years. We reviewed electronic health record data weekly to identify episodes of prescription opioid dose escalation; participants who had increases in their dose were seen for additional research visits within one month of dose escalation. Over two years, 19.5% of participants had prescription opioid dose increases. After controlling for covariates, there were no significant changes on any variable following dose escalation. Of those with a dose increase, 3% experienced a clinically meaningful improvement in pain following dose escalation. Participants in the entire sample had small improvements in pain intensity, depressive symptoms, medication-related side effects, and lower risk for prescription opioid misuse during the study period. Sexual functioning worsened over time. There were no significant changes in the full sample on pain disability, sleep functioning, or experiencing a fall. In summary, patients prescribed stable doses of long-term opioid therapy may demonstrate small changes in key pain-related outcomes over time, but prescription opioid dose escalation status is unrelated to clinical outcomes.
Learn More >Relaxation, biofeedback, and cognitive behavioral therapy are evidence-based behavioral therapies for migraine. Despite such efficacy, research shows that only about half of patients initiate behavioral therapy recommended by their headache specialists.
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