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Nerve-related (neuropathic) pain is a type of chronic pain that is associated with nerve damage. Neuropathic pain can be caused by many conditions, such as diabetes, sciatica, carpal tunnel syndrome or from adverse effects from chemotherapy. It causes a lot of suffering: the pain is more severe than non-nerve related pain (eg ankle sprain), people have lower quality of life, and in some people the pain may impact on their emotional wellbeing. Sadly, management of neuropathic pain remains a challenge; medications provide incomplete pain relief with often significant side effects.
Morton’s neuroma is a type of neuropathic pain, which is caused by compression and irritation of a nerve in the foot. Morton’s neuroma is special as it is sometimes treated with surgery: the injured nerve is taken out. This makes Morton’s neuroma a very interesting model system for researchers because they can directly study the injured human nerve.
A new study using Morton's neuroma as a unique model system, 'The local molecular signature of human peripheral neuropathic pain' was published this month in PAIN and has been selected as Editor’s choice. It is accompanied by a commentary by Ted Price and Jayden O’Brien, who are internationally eminent in the field.
our findings represent a shift in our field, as they show for the first time that intraneural inflammatory changes continue to play a role even in chronic neuropathic pain in humans'
In the study the team, led by Professor Annina Schmid, compared the nerve samples of 22 people with Morton’s neuroma with 11 nerves from people without nerve damage. They first analysed the molecular signature of the nerve samples by using RNA sequencing. This method allows them to see which genes are switched on or off inside the nerve. They found that many genes involved with the immune system are switched on in nerves from people with Morton’s neuroma compared to control nerves. This suggests that there is considerable inflammation inside a Morton’s neuroma.
Annina says 'our findings represent a shift in our field, as they show for the first time that intraneural inflammatory changes continue to play a role even in chronic neuropathic pain in humans'
Interestingly they identified a gene signature that is typical of a very specific type of immune cells called MGC macrophages. This gene signature correlated with patients’ neuropathic pain, suggesting that these may play a role in nerve pain. Staining techniques confirmed that there are indeed more of these MGC macrophages in Morton’s neuroma compared to control nerves.
Understanding these immune cells might ultimately help researchers find better treatments for nerve pain. Co-author of the paper Paul Chang adds that 'the discovery of a specific pain-related glucocorticoid-induced macrophage subtype could well have therapeutic potential.'