Background and aims
A significant role of the gastrointestinal microbiome in behavioural responses to opioids, including the development of tolerance has been suggested.
Morphine-induced neuro-immune interactions cause direct intestinal functional consequences. Meng et al. (2013) demonstrated that morphine disrupts gut barrier function via a toll-like receptors (TLR)-dependent manner. Low dose naltrexone (LDN) acts on various gut mechanisms

Methods
We have developed a treatment addressing gut brain axis interactions. 
We report the effect of a combination treatment consisting of:  Low dose naloxone (LDN), and pre probiotics aiming at a nutritional rehabilitation with focus on intestinal mucosa, microbiome and liver function and neuro-acupuncture on 10 patients with chronic refractory pain: fibromyalgia, multiple sclerosis, neurodegenerative disease, inflammatory bowel disease, endometriosis, postsurgical neuropathic pain, and post-traumatic stress syndrome.

Results
This approach resulted in pain relief, improved quality of sleep and quality of life with lower doses of analgesic drugs and reduction of the number of drug combinations, hence reducing the side effects.

Conclusions
Synergistic strategies acting on immune cells, glial cells and neurons, synaptic plasticity and pain are promising.
Current concepts of gut-brain interaction in analgesic tolerance to opioids suggest that peripheral mechanisms emanating from the gut can profoundly affect central control of opioid function.
Genetic variations may modulate the answer to treatment as does the inter-individual differences in the bacterial flora of the human digestive tract. Rapid progress in the understanding of the host microbial interaction has redefined pharmacokinetics of drug metabolism, allowing to improve the management of drug (ab) users.

WHEN OPIOIDS FAIL IN CHRONIC PAIN MANAGEMENT: THE INTESTINAL EPITHELIAL BARRIER: A THERAPEUTIC TARGET?