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Background and Aims Post-traumatic chronic pain (PTCP) is defined as persisting pain beyond the healing process after injury. Multiple drug intolerance syndrome (MDIS) is an under-reported condition that may restrict treatment of several diseases. We present a case of PTCP complicated by multiple drug allergies and intolerances.Results A 53-year-old woman was referred to our Pain Medicine Unit in 2019 due to refractory right cervicobrachialgy and cervicogenic headache, initiated after traumatic brain injury with cervical trauma in 2015. She mentioned adverse effects to multiple drugs, including anaphylaxis. After referral to Immunoallergology, allergies to morphine, lidocaine and methylprednisolone were confirmed. She also developed intolerance to drugs from different pharmacological classes: antidepressants, gabapentinoids and opioids. She was referred to Genetic Medicine, with pharmacogenomic study revealing no significant findings to modify pain therapy. Genetic testing excluded monogenic allergic diseases, but detected the RYR1 gene pathogenic variant associated with malignant hyperthermia susceptibility. Her treatment included non-pharmacologic strategies as physical therapy and acupuncture, with incomplete pain relief. Invasive procedures were also performed: ultrasound guided right suprascapular nerve block; posterior serratus, teres major and occipital fascial plane injections; greater occipital nerve block; cervical trigger point injections. She had functional improvement afterwards, however myofascial syndrome persists with quality of life impairment and need for a multidisciplinary approach. Additional invasive procedures are being planned to achieve longer lasting effect.Conclusions PTCP treatment is complex, especially when patients present adverse effects to several pharmacological classes. Multidisciplinary approaches should be used in these cases. Immunoallergology added valuable information, confirming safety of the drugs in use. Genetic testing is useful in MDIS cases with refractory chronic pain. Although in this case no gene related allergic diseases were identified, the RYR1 pathogenic variant was a relevant finding. Invasive procedures’ aim is a longer lasting pain relief with a lower need for medications that patients may not tolerate.