Tramadol was mutagenic in the presence of metabolic activation inside mouse lymphoma assay. Tramadol wasn’t mutagenic in the in vitro bacterial reverse mutation assay using Salmonella and E. coli (Ames), the mouse lymphoma assay inside the absence of metabolic activation, the in vitro chromosomal aberration assay, or even the in vivo micronucleus assay in bone marrow.

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Chronic opioid use can lead to long-term repeated activation of mu opioid receptors inside myenteric and submucosal plexi with subsequent uncoordinated bowel activity, and resultant opioid-induced bowel dysfunction (17). Opioids reduce peristalsis via decreasing gastrointestinal secretions and relaxing longitudinal muscle in the colon along with simultaneously/increasing contractions of the circular muscles (15). Stool may dry and harden due to deficiency of longitudinal propulsion and increased circular muscle activity increase the tone with the bowel with resultant impaired gastrointestinal motility, bowel distention and cramping (18) which might be associated with nausea and/or vomiting.

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