Pain and Opioid-Induced Gut Microbial Dysbiosis

Abstract

Opioid-induced dysbiosis (OID) is a specific condition describing the consequences of opioid use on the bacterial composition of the gut. Opioids have been shown to affect the epithelial barrier in the gut and modulate inflammatory pathways, possibly mediating opioid tolerance or opioid-induced hyperalgesia; in combination, these allow the invasion and proliferation of non-native bacterial colonies. There is also evidence that the gut-brain axis is linked to the emotional and cognitive aspects of the brain with intestinal function, which can be a factor that affects mental health. For example, Mycobacterium, Escherichia coli and Clostridium difficile are linked to Irritable Bowel Disease; Lactobacillaceae and Enterococcacae have associations with Parkinson’s disease, and Alistipes has increased prevalence in depression. However, changes to the gut microbiome can be therapeutically influenced with treatments such as faecal microbiota transplantation, targeted antibiotic therapy and probiotics. There is also evidence of emerging therapies to combat OID. This review has collated evidence that shows that there are correlations between OID and depression, Parkinson’s Disease, infection, and more. Specifically, in pain management, targeting OID deserves specific investigations.

The Association between Dysbiosis and Neurological Conditions Often Manifesting with Chronic Pain

“…The composition of the microbiota varies at different locations of the GIT and is affected by oxygen, chemical, endogenous antimicrobials, nutritional and immunological features of the gut [ 14 ]. Dysbiosis of this system is a change in the resident microbiota and reduced microbial diversity, which disrupts gut homeostasis, ultimately having varied negative impacts on the host [ 11 ]. Alterations in GIT microbiota impacts immune system activity, metabolic disorders, including diabetes, insulin resistance, inflammation and dyslipidaemia, and impacts endocrine regulation [ 31 ].…”

“…Indeed, studies have shown that commonly used drugs, including antipsychotics, proton-pump inhibitors (PPIs), hormones and anticancer drugs have a deleterious impact on microbial species of the GIT [ 21 ]. Opioid-induced dysbiosis has been associated with dysbiosis associated disease states and opioid tolerance [ 11 ]. Interestingly, Metformin, a therapeutic for the treatment of T2D, has recently been shown to alter the gut microbial diversity [ 21 ].…”

“…While the use of opioids for long-term treatment of pain does not appear effective in reducing pain levels [ 7 ], the risks associated with opioid use include opioid tolerance, diversion, addiction, overdose and death [ 10 ]. Opioid-induced hyperalgesia is associated with increased chronic pain symptoms as it leads to central sensitization, neuroinflammation and worsening pain symptoms in patients prescribed opioid analgesics [ 11 ]. Importantly, patients of chronic pain also have increased rates of suicide ideation, attempts and successful suicides [ 12 ].…”

Short-Chain Fatty Acids in the Microbiota–Gut–Brain Axis: Role in Neurodegenerative Disorders and Viral Infections

“…48 By extensive literature survey, we came to the understanding that the relationship between pain pathways and GI microbiota is still unclear with limited experimental evidence. 35,49 3.2. Bottom-Up Signaling (Gut to Brain).…”

Microbiological and Physiological Effects of Pain

“…Neuroinflammation can occur if nociceptor-induced inflammation extends over a larger area than was originally included in receiving the nociceptive stimulus and when other proinflammatory cytokines, such as interleukin (IL)-1b, IL-6, IL-8, and tumor necrosis factor-alpha (TNFα), are released. The altercation of vascular permeability resulting in the activation of microglia and astrocytes is also involved in this type of inflammation [ 30 ]. It has been proposed that mannose receptor C-type 1 (MRC1 +) spinal macrophages are responsible or limiting neuroinflammation and resolving mechanical pain that follows noxious stimuli from an injury [ 31 ].…”