by Dr. Al Al-Alhaidari
Neuropathic pain
Neuropathic pain is one of the most common chronic non cancer pain conditions
What is neuropathic pain?
Neuropathic pain is caused by damage or injury to the nerves that transfer information between the brain and spinal cord from the skin, muscles and other parts of the body.
The pain is usually described as a burning sensation and affected areas are often sensitive to the touch. Symptoms of neuropathic pain may also include excruciating pain, pins and needles, difficulty correctly sensing temperatures and numbness. Some people may find it hard to wear thick clothes as even slight pressure can aggravate the pain.
Common causes of neuropathic pain include nerve pressure or nerve damage after surgery or trauma, viral infections, cancer, vascular malformations, alcoholism, neurological conditions such as multiple sclerosis and metabolic conditions such as diabetes. It may also be a side effect of certain medications. Occasionally no identifiable cause is found which can be distressing for the individual experiencing the pain.
Chronic neuropathic pain is common and may be related to an underlying health condition such as cancer or diabetic neuropathy, or it could be related to treatments such as chemotherapy.
Neuropathy pathophysiology:
The neurotransmitters and aberrant synapses involved in the pain pathways are diffuse. After peripheral nerve lesions, aberrant regenerative synapses may occur leading to spontaneously firing neurons producing allodynia and/or hyperalgesia. Peripheral nerve damage induces glial cells to release pro-inflammatory cytokines and glutamate, an NMDA receptor agonist . With chronic nerve injury, redistribution of sodium and calcium channels can result in spontaneous firing of the neuron deemed peripheral sensitization . Loss of afferent signals and peripheral sensitization can induce functional changes in the dorsal horn leading to central sensitization . The activation and upregulation of dorsal horn excitatory NMDA receptors is believed to play a central role in neuropathic pain, allodynia and hyperalgesia. NMDA receptor antagonism results in analgesia by preventing central sensitization in dorsal horn neurons .
Management of neuropathic pain:
As we know, Millions of Canadian live with moderate to severe chronic pain. prevalence of chronic pain with neuropathic components range between 6% and 10%. We’ve been using different management models over long time for neuropathic pain to reach best results. The current medical guideline for neuropathic pain including ;tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, gabapentanoids, topicals, and transdermal substances. Those medications are first and second line of treatment.Cannabis is one of those models and still in use too.
Ketamine for neuropathic pain:
Ketamine is a potent NMDA antagonist which is frequently used in the treatment of acute and chronic pain, sedation, induction and maintenance of anesthesia,ketamine's ability to inhibit NMDA receptor, ketamine can help treat chronic neuropathic pain . Additionally, ketamine has been shown to be a rapid acting antidepressant, making it useful in the concomitant treatment of pain and depression.Ketamine is a promising treatment for chronic neuropathic pain. The current understanding of neuropathic pain pathophysiology highlights ketamine's potential to treat this difficult illness.
NMDA blocker researches:
These new searches motivated pain management centers and researchers to conduct multiple studies to assess NMDA blocker and their effect in neuropathic pa. Multiple researches and studies(58) were systemic reviewed by Rohit Aiyer, MD ad his colleagues .Medication mostly in all those studies were( Ketamine, Methadone, Memantine, Amantadine,Dextrometharphine ).
systemic review the trials for ketamine, 15 showed some benefit for analgesia. Methadone had 3 positive trials, while amantadine and memantine each only had 2 trials showing neuropathic pain analgesic properties. Dextromethorphan had 1 randomized controlled trials that showed some neuropathic pain treatment benefit.
over 15 of the studies for Ketamine showed some type of benefit for neuropathic pain relief. Topical application gave relatively poor results in pain reduction, with only Finch et al4 giving positive results for this route being efficacious.. Orally, Ketamine also only produce 1 clinically efficacious result,5. Many studies analyzed were of IV administration, with all of the IV studies showing some type of analgesic effect. More importantly, the results that Ketamine was able to produce varied among the pathologies, from spinal cord injury (SCI) to PLP to complex regional pain syndrome.
Patients on IV Ketamine reported less neuropathic pain symptoms by 50% when it was compared to patients who received Lidocaine.Pain score was assessed with VAS.
Methadone has r trials and studies and result were showing a split response clinically for treatment of neuropathic pain, with 3 showing some analgesic benefit while the other 3 did not.one study was unable to show Methadone was better efficacy compared with oral Ketamine for neuropathic pain.6.However, Methadone was better when compared head to head with fentanyl for chronic neuropathic pain. 7
Amantadine 6 studies on diabetic neuropathy showed fairly positive clinical benefit, which include 4 studies while 2 did not show any benefit.While Memantine 7 studies for treatment of neuropathic pain, only 2 showed any clinical benefits for the patient.
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