The Guts of the Opioid Crisis

Bidirectional interactions of the gut epithelium with commensal bacteria are critical for maintaining homeostasis within the gut. Chronic opioid exposure perturbs gut homeostasis through a multitude of neuro-immune-epithelial mechanisms, resulting in the development of analgesic tolerance, a major underpinning of the current opioid crisis. Differences in molecular mechanisms of opioid tolerance between the enteric and central pain pathways pose a significant challenge for managing chronic pain without untoward gastrointestinal effects.

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Activation of Central Pain Pathways in Rheumatic Diseases: What We have Learned from Functional Neuroimaging Studies

Current Rheumatology Reviews ◽

10.2174/157339710791792694 ◽

2010 ◽

Vol 6 (3) ◽

pp. 208-215

Author(s):

Nidhi Sofat ◽

Philip Hamann ◽

Thomas R. Barrick ◽

Franklyn A. Howe

Keyword(s):

Rheumatic Diseases ◽

Functional Neuroimaging ◽

Central Pain ◽

Pain Pathways

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Antiepileptic and Antidepressant Drugs Used in the Treatment of Pain

10.2310/pm.15092 ◽

2017 ◽

Author(s):

Lucia Daiana Voiculescu

Keyword(s):

Serotonin Syndrome ◽

Molecular Mechanisms ◽

Tricyclic Antidepressants ◽

Antidepressant Drugs ◽

First Line ◽

Off Label ◽

First Line Therapy ◽

Line Therapy ◽

Pain Pathways ◽

Different Levels

Antiepileptics and antidepressants are two categories of drugs frequently used as adjuvant analgesics. They interfere with the pain pathways at different levels through complex and not always well-defined molecular mechanisms. Although only a few have been licensed for use in the treatment of certain types of pain, anticonvulsants and antidepressants are widely prescribed off-label for pain associated with a variety of conditions. Most solid data come from experience with their use for postherpetic neuralgia, pain associated with diabetic neuropathy, and fibromyalgia. Anticonvulsants and antidepressant drugs are frequently used as first-line therapy in the treatment of pain, especially neuropathic type. Key words: antidepressant drugs, antiepileptic drugs, carbamazepine, gabapentinoids, neuropathic pain, off-label use, serotonin-norepinephrine reuptake inhibitors, serotonin syndrome, tricyclic antidepressants, use in specific populations

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The effects of propranolol on heart rate variability and quantitative, mechanistic, pain profiling: a randomized placebo-controlled crossover study

Scandinavian Journal of Pain ◽

10.1515/sjpain-2018-0054 ◽

2018 ◽

Vol 18 (3) ◽

pp. 479-489 ◽

Cited By ~ 6

Author(s):

Kristian Kjær Petersen ◽

Hjalte Holm Andersen ◽

Masato Tsukamoto ◽

Lincoln Tracy ◽

Julian Koenig ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Chronic Pain ◽

Pain Sensitivity ◽

Experimental Pain ◽

Central Pain ◽

Healthy Male ◽

Pain Pathways ◽

Β Blocker ◽

Chronic Pain Conditions

AbstractBackground and aimsThe autonomic nervous system (ANS) is capable of modulating pain. Aberrations in heart rate variability (HRV), reflective of ANS activity, are associated with experimental pain sensitivity, chronic pain, and more recently, pain modulatory mechanisms but the underlying mechanisms are still unclear. HRV is lowered during experimental pain as well as in chronic pain conditions and HRV can be increased by propranolol, which is a non-selective β-blocker. Sensitization of central pain pathways have been observed in several chronic pain conditions and human mechanistic pain biomarkers for these central pain pathways include temporal summation of pain (TSP) and conditioned pain modulation (CPM). The current study aimed to investigate the effect of the β-blocker propranolol, and subsequently assessing the response to standardized, quantitative, mechanistic pain biomarkers.MethodsIn this placebo-controlled, double-blinded, randomized crossover study, 25 healthy male volunteers (mean age 25.6 years) were randomized to receive 40 mg propranolol and 40 mg placebo. Heart rate, blood pressure, and HRV were assessed before and during experimental pain tests. Cuff pressure pain stimulation was used for assessment of pain detection (cPDTs) and pain tolerance (cPTTs) thresholds, TSP, and CPM. Offset analgesia (OA) was assessed using heat stimulation.ResultsPropranolol significantly reduced heart rate (p<0.001), blood pressure (p<0.02) and increased HRV (p<0.01) compared with placebo. No significant differences were found comparing cPDT (p>0.70), cPTT (p>0.93), TSP (p>0.70), OA-effect (p>0.87) or CPM (p>0.65) between propranolol and placebo.ConclusionsThe current study demonstrated that propranolol increased HRV, but did not affect pressure pain sensitivity or any pain facilitatory or modulatory outcomes.ImplicationsAnalgesic effects of propranolol have been reported in clinical pain populations and the results from the current study could indicate that increased HRV from propranolol is not associated with peripheral and central pain pathways in healthy male subjects.

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Anti-nociceptive Effect of Caralluma edulis on Peripheral and Central Pain Pathways

Sains Malaysiana ◽

10.17576/jsm-2017-4610-24 ◽

2017 ◽

Vol 46 (10) ◽

pp. 1859-1863 ◽

Cited By ~ 1

Author(s):

Sundas Firdoos ◽

Arif-Ullah Khan ◽

Fawad Ali

Keyword(s):

Central Pain ◽

Pain Pathways

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Central Pain Pathways

Encyclopedia of Pain ◽

10.1007/978-3-642-28753-4_200335 ◽

2013 ◽

pp. 537-537

Keyword(s):

Central Pain ◽

Pain Pathways

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Dysfunctional peroxisomes compromise gut structure and host defense by increased cell death and Tor-dependent autophagy

Molecular Biology of the Cell ◽

10.1091/mbc.e18-07-0434 ◽

2018 ◽

Vol 29 (22) ◽

pp. 2766-2783 ◽

Cited By ~ 9

Author(s):

Francesca Di Cara ◽

Margret H. Bülow ◽

Andrew J. Simmonds ◽

Richard A. Rachubinski

Keyword(s):

Cell Death ◽

Host Defense ◽

Redox Balance ◽

Gut Epithelium ◽

Obesity And Diabetes ◽

Gut Homeostasis ◽

Survival And Development ◽

Gut Microbe ◽

Tor Kinase ◽

Immune Pathways

The gut has a central role in digestion and nutrient absorption, but it also serves in defending against pathogens, engages in mutually beneficial interactions with commensals, and is a major source of endocrine signals. Gut homeostasis is necessary for organismal health and changes to the gut are associated with conditions like obesity and diabetes and inflammatory illnesses like Crohn’s disease. We report that peroxisomes, organelles involved in lipid metabolism and redox balance, are required to maintain gut epithelium homeostasis and renewal in Drosophila and for survival and development of the organism. Dysfunctional peroxisomes in gut epithelial cells activate Tor kinase-dependent autophagy that increases cell death and epithelial instability, which ultimately alter the composition of the intestinal microbiota, compromise immune pathways in the gut in response to infection, and affect organismal survival. Peroxisomes in the gut effectively function as hubs that coordinate responses from stress, metabolic, and immune signaling pathways to maintain enteric health and the functionality of the gut–microbe interface.

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