How Genetics Can Complicate Pain Treatment
A 37-year-old white male was referred for pain treatment by a physician in a local methadone clinic. The patient’s pain started 3 years earlier when he suffered an industrial injury while pulling a heavy, electric cable. A series of epidural corticosteroid injections, physical therapy, and transcutaneous electrical nerve stimulation (TENS) did not provide pain relief. His pain was so severe that standard dosages of hydrocodone were ineffective. The patient could not find a physician to prescribe a more potent opioid, so he enrolled in a local methadone maintenance program for pain relief. The physician in the methadone clinic recognized that the patient was mistakenly enrolled in the clinic for pain treatment rather than opioid addiction.
The patient described his pain as constant unless he was sleeping, and he needed to take a sedative to sleep. The pain was centered in the lumbar area and radiated into the buttocks and upper legs. His pain was so severe that he was bed-bound most of the time.
When asked about prior medical history, the patient said he required extra anesthesia for dental procedures. His daily dose of methadone (75 mg) would only provide pain relief for 2 to 4 hours. In addition, he only received 1 to 2 hours of pain relief with hydrocodone compounds, and he had to take a high dose to experience any pain relief. He had no known genetic diseases, but his mother did not experience pain relief when she took hydrocodone. He did not drink alcohol. As a teenager, he became extremely ill and vomited when he first drank alcohol. When he did drink, he had to drink more than his friends to feel alcohol’s effects. There were no claimed allergies.
Review of Medical Records
A magnetic resonance imaging scan of the lumbar spine showed disc bulges at L4-L5 and L5-L6, as well as foraminal stenosis. His left femoral head had a
deformity with a question of prior fracture.
Physical examination revealed a healthy young adult male. He walked, however, with a cane and dragged his left foot. His right leg had diminished strength and reflexes. There was considerable asymmetry of his spine muscles. His left shoulder drooped about 1 inch below the right.
The patient has been seen by multiple orthopedic and neurosurgeons who did not consider him a surgical candidate. Prior medications for pain control included anti-depressants, anti-convulsants, anti-inflammatory drugs, and the opioids codeine, propoxyphene, and tramadol. At the time of referral, the treatment options included:
- Refer patient to addiction-methadone treatment.
- Switch medications from opioids to non-narcotic medications.
- Place the patient on around-the-clock methadone, combined with opioids for breakthrough pain.
- Leave the patient on methadone and try epidural corticosteroid injections.
Options 1, 2, and 4 were rejected because the patient had previously attempted and failed non-opioid and weak-opioid treatments, epidural injections, and his pain was inadequately controlled with his current treatment plan. The patient rejected, out-of-hand, detoxification. The option chosen (option 3) was to simply find a treatment plan that allowed him to physically and mentally function to the point where he could increase his daily activities.
The patient was initially treated with around-the-clock administration of methadone 20 mg given in 4 separate dosages, plus hydrocodone 10 mg or hydromorphone 8 mg for breakthrough pain. This regimen provided enough pain relief so that the patient was able to increase his daily activities.
A variety of opioids have been attempted over a follow-up period of 10 years. They have included oxycodone, morphine, and fentanyl. Only the combination of the fentanyl transdermal patch with methadone gave the patient pain relief for more that 1 to 2 hours. His current daily opioid dosage has been stable for the past year: fentanyl transmucosal 2,400 µg, fentanyl transdermal 2,400 µg, and methadone 200 mg. Opioid blood level testing documented a very high fentanyl level of 16.4 ng/mL and methadone of 347 ng/mL.
Cytochrome P450 testing showed that the patient has a CYP2C9 genetic defect—he cannot normally metabolize many drugs, including opioids. Despite his need for a high-dose opioid regimen and his genetic defect, he now has a full-time job.
A healthy appearing young male can have a difficult time obtaining pain treatment. He may mistakenly develop the label “addict” or “pseudo-addict” because he must constantly ask medical providers for help. This particular patient was so unsuccessful with his initial treatment plan that he had to seek pain relief in a methadone program for heroin addicts.
The finding of a CYP2C9 defect likely explains many of the difficulties in treating this patient. To obtain adequate pain relief to function, the patient was prescribed 2 long-acting opioids: a fentanyl transdermal patch and oral methadone. Apparently, these 2 opioids, when combined, produce high enough opioid blood levels to force or bypass a genetically defective enzyme system. Genetic screening for defects in opioid metabolism may be very appropriate in patients who complain that their current treatment plan doesn’t provide adequate pain relief.