Najib Babul – Opioids for Neuropathic Pain: Worth the Risk?
Published on December 29, 2016 by Dr. Najib Babul
Neuropathic pain is pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, or put more simply, pain due to injury to sensory nerves. Neuropathic pain can be broadly divided into peripheral neuropathic pain and central neuropathic pain. Until relatively recently, a limited number of older tricyclic antidepressants and anti-epileptics had demonstrated efficacy in peripheral neuropathic pain but none were approved by the FDA for this purpose. Presently, clinicians treat neuropathic pain using one of many different classes of drugs, including opioid analgesics. In this brief post intended for a general audience, Dr. Najib Babul shares his thoughts on the potential benefits and limitations of prescribing opioids for neuropathic pain.
Painful diabetic neuropathy and painful HIV-associated neuropathy are characterized by burning sensations in the soles of the feet, as well as paresthesia (“pins and needles”) of the dorsum and soles of the feet. Postherpetic neuralgia on the other hand is due to nerve damage caused by the varicella zoster (chicken pox) virus after a herpes zoster (shingles) infection. Postherpetic neuralgia involves the skin over the thoracic, trigeminal and cervical spinal nerves. Other examples of peripheral neuropathic pain include chemotherapy associated neuropathic pain, post-amputation neuropathic pain and post-traumatic neuropathic pain. Examples of central neuropathic pain include post-stroke pain, spinal cord injury pain and multiple sclerosis-associated pain. Neuropathic pain can be ongoing or steady pain superimposed by brief or shooting pain and allodynia (pain upon light non-painful touch).
Although opioid analgesics have been used to treat neuropathic pain for many decades, their use was restricted to severe neuropathic pain that was unresponsive to other drugs. There was considerable skepticism about the efficacy of opioids for neuropathic pain Neuropathic pain was thus viewed by some as “opioid resistant” and when effective, it was thought to require much higher doses of opioids. Initial suggestions of the potential benefits of chronic opioid therapy came from Dr. Michael Rowbotham’s elegant single-dose morphine infusion study which showed pain relief for at least 2-hours after a one-hour infusion (Neurology. 1991;41:1024-8).
“Dr. Rowbotham’s study provided the impetus for our own four-week randomized placebo controlled clinical trial of extended-release oxycodone or OxyContin® (Watson & Babul, Neurology 1998;50:1837-41) which demonstrated for the first time that chronic therapy with opioids such as OxyContin could provide significant and sustained reductions in ongoing pain, shooting pain and allodynia in patients with postherpetic neuralgia”, noted Dr. Najib Babul. The magnitude of pain relief observed with extended-release oxycodone in our study was at least comparable if not superior to that demonstrated with other drugs. Since then, extended-release oxycodone has also demonstrated efficacy over placebo in painful diabetic neuropathy (Watson CPN, et al. Pain. 2003; 105:71-8). It is thought that the results with extended-release oxycodone are likely generalizable to other strong opioids (Rowbotham et al. N Engl J Med. 2003; 348:1223-32). In the published work with extended-release oxycodone in peripheral neuropathic pain, side effects included nausea, vomiting, drowsiness, fatigue, dry mouth and constipation, consistent with its pharmacology. However, clinical trials tend to be of short duration and they are conducted in controlled environment with careful patient selection. This is usually not reflective of eventual post-marketing use in a less controlled settings and with a more heterogeneous population. Therefore, many clinicians have continued reticence to prescribing opioids for neuropathic pain. Chief among their concerns are the durability of pain relief, and perhaps more importantly, the risk of iatrogenic addiction and diversion into illicit distribution channels for eventual non-medical use. Najib Babul, PharmD, MBA
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