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Emotional disorders are common comorbid conditions that further exacerbate the severity and chronicity of chronic pain. However, individuals show considerable vulnerability to developing chronic pain under similar pain conditions. In this study on male rat and mouse models of chronic neuropathic pain, we identify the histone deacetylase SIRT1 in central amygdala as a key epigenetic regulator that controls the development of comorbid emotional disorders underlying the individual vulnerability to chronic pain. We found that animals that were vulnerable to developing behaviors of anxiety and depression under the pain condition displayed reduced SIRT1 protein in central amygdala, but not those animals resistant to the emotional disorders. Viral overexpression of local SIRT1 reversed this vulnerability, but viral knockdown of local SIRT1 mimicked the pain effect, eliciting the pain vulnerability in pain-free animals. The SIRT1 action was associated with CaMKIIα downregulation and deacetylation of histone H3 lysine 9 at the promoter. These results suggest that, by transcriptional repression of in central amygdala, SIRT1 functions to guard against the emotional pain vulnerability under chronic pain conditions. This study indicates that SIRT1 may serve as a potential therapeutic molecule for individualized treatment of chronic pain with vulnerable emotional disorders.Chronic pain is a prevalent neurological disease with no effective treatment at present. Pain patients display considerably variable vulnerability to developing chronic pain, indicating individual-based molecular mechanisms underlying the pain vulnerability, which is hardly addressed in current preclinical research. In this study, we have identified the histone deacetylase Sirtuin 1 (SIRT1) as a key regulator that controls this pain vulnerability. This study reveals that the SIRT1–CaMKIIaα pathway in central amygdala acts as an epigenetic mechanism that guards against the development of comorbid emotional disorders under chronic pain, and that its dysfunction causes increased vulnerability to developing chronic pain. These findings suggest that SIRT1 activators may be used in a novel therapeutic approach for individual-based treatment of chronic pain.
Learn More >Slow deep breathing (SDB) is commonly employed in the management of pain, but the underlying mechanisms remain equivocal. This study sought to investigate effects of instructed breathing patterns on experimental heat pain and to explore possible mechanisms of action. In a within-subject experimental design, healthy volunteers (n = 48) performed four breathing patterns: 1) unpaced breathing (UB), 2) paced breathing at the participant's spontaneous breathing frequency (PB), 3) SDB at six breaths per minute with a high inspiration/expiration ratio (SDB-H), and 4) SDB at six breaths per minute with a low inspiration/expiration ratio (SDB-L). During presentation of each breathing pattern, participants received painful heat stimuli of three different temperatures and rated each stimulus on pain intensity. Respiration, heart rate, and blood pressure were recorded. Compared to UB, participants reported less intense pain during each of the three instructed breathing patterns. Among the instructed breathing patterns, pain did not differ between PB and SDB-H, and SDB-L attenuated pain more than the PB and SDB-H patterns. The latter effect was paralleled by greater blood pressure variability and baroreflex effectiveness index during SDB-L. Cardiovascular changes did not mediate the observed effects of breathing patterns on pain. Perspective: SDB is more efficacious to attenuate pain when breathing is paced at a slow rhythm with an expiration that is long relative to inspiration, but the underlying mechanisms remain to be elucidated.
Learn More >Major depressive disorders (MDD) and chronic pain (CP) affect significant portion of the world's population and have high comorbidity rate. Social defeat stress (SDS) model was standardized in mice and can trigger depressive-like behavior and chronic pain. Based especially on clinical trials showing an effective preventive and therapeutic effect of physical exercise on CP and symptoms associated with MDD, this study aimed to investigate if the voluntary running wheel exercise can exert these effects in mice submitted to the 10-day SDS protocol, using fluoxetine as positive control. For this, we ran two set of experiments: in the first set mice started performing voluntary running wheel exercise after submitted to SDS and, in the second set, mice performed voluntary running wheel exercise before and during SDS. Mechanical and chemical hyperalgesia was analyzed through electronic von Frey and capsaicin test, respectively. Depressive-like behavior was assessed through social interaction test. Our results showed that the voluntary running wheel exercise was more effective than fluoxetine reversing the SDS-induced persistent hyperalgesia and both, fluoxetine and voluntary running wheel exercise, was effective reversing SDS-induced social avoidance. Also, voluntary running wheel exercise is an effective tool preventing both hyperalgesia and social avoidance induced by SDS. To the best of our knowledge, this was the first study using physical exercise as a therapeutic and preventive tool for chronic pain and depressive-like behavior simultaneously induced by social stress.
Learn More >The opioid crisis has highlighted the importance of improving patients' access to behavioral treatments for chronic pain and addiction. What is not known is if patients are interested in receiving these treatments. In this cross-sectional study, over 1000 participants with chronic pain were surveyed using an anonymous online questionnaire on Amazon Mechanical Turk (Mturk) to investigate participants' use of and interest in pharmacological and behavioral treatments for chronic pain and addiction. Participants also indicated whether their doctor had recommended these treatments. The majority of participants reported using medication for their pain (83.19%) and that their doctor recommended medication (85.05%), whereas fewer participants reported using (67.45%) and being recommended to (62.82%) behavioral treatments. We found 63.67% of participants screened positive for possible opioid misuse; those who screened positive were more interested in receiving behavioral treatments than those who did not screen positive. Participants who received treatment recommendations were more likely to be interested in receiving those treatments as compared to participants who did not. The results suggest that recommendations for behavioral treatments and interest in those treatments are related. Results also suggest that patients endorsing behaviors consistent with opioid misuse are interested in behavioral treatments. Perspective: This study provides information around chronic pain patients' treatment interests, treatment receipt, and recommendation receipt for behavioral pain management and addiction treatment. This study could help facilitate communication between patients and doctors regarding available treatments for chronic pain and pain treatment-related addiction problems.
Learn More >Do measures of state anxiety and trait anxiety in people with acute low back pain (ALBP) improve prediction of chronic low back pain (CLBP), defined as pain or pain-related disability at 12 weeks?
Learn More >Learned helplessness develops with prolonged exposure to uncontrollable stressors and is therefore germane to individuals living with pain or other poorly controlled chronic diseases. This study has developed a helplessness scale for chronic conditions distinct from previous scales that blur the conceptualization of control constructs. Extant measures commonly examine controllability, not the three pillars of helplessness identified by Maier and Seligman (1976): cognitive, emotional, and motivational/motor deficits.
Learn More >The incidence and severity of chronic postoperative pain (POP) are major clinical challenges, and presurgical conditioned pain modulation (CPM) and pain catastrophizing scale (PCS) assessments have exhibited predictive values for POP. However, whether CPM and PCS assessments are also predictive of acute POP is unknown.
Learn More >Previous studies on the association between weather and pain severity among patients with chronic pain have produced mixed results. In part, this inconsistency may be due to differences in individual pain responses to the weather.
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