NMDA receptor antagonists for neuropathic pain

N-methyl-d-aspartate (NMDA) receptor antagonists (e.g. ketamine, dextromethorphan, memantine, and amantadine) may have a role in the management of neuropathic pain. These agents are increasingly used by specialists who manage neuropathic pain e.g. in pain clinics and specialist palliative care clinics.(1)

• Ketamine is generally used as an anaesthetic
  • however at sub-anaesthetic doses it acts as an analgesic by blocking the NMDA receptor in the dorsal horn
  • the NMDA receptor is thought to be activated in clinical states where hyper-analgesia and allodynia are present
  • often ketamine is administered parenterally

Note - a number of pharmacological treatments can be used to manage neuropathic pain outside of specialist pain management services. However, there is considerable variation in how treatment is initiated, the dosages used and the order in which drugs are introduced, whether therapeutic doses are achieved and whether there is correct sequencing of therapeutic classes. A further issue is that a number of commonly used treatments are unlicensed for treating neuropathic pain, which may limit their use.

Current NICE guidance states that for the treatment of all neuropathic pain (except trigeminal neuralgia), offer a choice of amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment. (2)

If the initial treatment is not effective or is not tolerated, offer 1 of the remaining 3 drugs, and consider switching again if the second and third drugs tried are also not effective or not tolerated.

Consider tramadol only if acute rescue therapy is needed.

Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments.

Do not start the following to treat neuropathic pain in non-specialist settings unless advised by a specialist to do so:

• cannabis sativa extract
• capsaicin patch
• lacosamide
• lamotrigine
• levetiracetam
• morphine
• oxcarbazepine
• topiramate
• tramadol (this is referring to long-term use)
• venlafaxine
• valproate (follow the MHRA safety advice on valproate use in women and girls).

Reference:

1. Chirita C et al. Exploring the Therapeutic Potential of N-Methyl-D-Aspartate Receptor Antagonists in Neuropathic Pain Management. Int. J. Mol. Sci. 2024, 25(20), 11111
2. NICE. Neuropathic pain in adults: pharmacological management in non-specialist settings. Clinical guideline CG173. Published November 2013, last updated September 2020