Prevalence of neuropathic pain is high after major surgery. However, effective treatment for preventing neuropathic pain is lacking.

Here we report that perisurgical treatment of neuroprotectin D1/protectin D1 (NPD1/PD1), derived from docosahexaenoic acid, prevents nerve injury-induced mechanical allodynia and ongoing pain in mice.

Intrathecal post-treatment of NPD1/PD1 also effectively reduces established neuropathic pain and produces no apparent signs of analgesic tolerance. Mechanistically, NPD1/PD1 treatment blocks nerve injury-induced long-term potentiation, glial reaction, and inflammatory responses, and reverses synaptic plasticity in the spinal cord.

Thus, NPD1/PD1 and related mimetics might serve as a new class of analgesics for preventing and treating neuropathic pain.

Neuroprotectin/protectin D1 protects against neuropathic pain in mice after nerve trauma, by ZZ Xu et al, in Ann Neurol 2013 Sep; 74(3):490-5.

Comment by Cort Johnson:


From opioids to anticonvulsants to antidepressants, etc. doctors throw a wide variety of drugs at nerve pain, yet the prognosis is generally poor with 40-60% of patients receiving only partial relief. (Some studies indicate alpha lipoic acid and benfotiamine (thiamine) can be helpful for some, as well.)

Reducing the inflammation in the nervous system could reduce the difficult to treat nerve pain as well. Nerve pain comes in many shades and can produce burning, tingling, numbness, shooting, stabbing, allodynia, etc. Usually associated with central sensitization ( increased pain sensitivity), inflammation in the brain/spinal column appears to play a significant role but few drugs are effective at reducing inflammation there.

Lyrica’s incredible success, in spite of issues with side effects and efficacy, highlights the great need for better means of dealing with neuropathic pain. Increasing restrictions on opioid use makes the development of more effective means of pain relief imperative. In the next couple of blogs we’re going to look at two drugs under development that may help at some point.

Probably the most intriguing is a compound called neuroprotectin D1 (NPD1) – the subject of increasingly intense investigation. NPDI has been mostly investigated as a protective agent in central nervous system, eye and kidney disorders but a recent study suggested it may be effective against the hardest to treat pain of all; nerve pain. Enter a potentially cheap drug derived from a fatty acid often used in chronic fatigue syndrome and fibromyalgia.

Derived from DHA, an omega-3 fatty acid found in fish oils… In contrast to omega-6 fatty acids which have pro-inflammatory effects, omega-3 fatty acids have anti-inflammatory effects.

Studies have not generally borne out their efficacy in ME/CFS but they are commonly recommended and used. With NDPI clocking in at about 1,000 times the potency of its precursor, DHA, NPDI – if it ever gets to market – will be like fish oil on speed. NDPI is potentially much more than a pain reliever; indeed, pain is only the latest symptom NDPI is being thrown at. An aptly named drug, neuroprotectin D1 is produced in response to a variety of conditions, some of which occur in chronic fatigue syndrome and fibromyalgia, including oxidative stress (high in ME/CFS/FM), protein misfolding (perhaps occurring in ME/CFS), seizures and brain ischemia-reperfusion (conjectured to occur in ME/CFS/FM).

Drug Under Development Spells Hope for Pain in Fibromyalgia and Chronic Fatigue Syndrome, by Cort Johnson

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