If no underlying cause for the small fibre neuropathy is found, treatment will be directed towards alleviation of symptoms. This can be done with medication and/or pain rehabilitation.

For drug treatment of neuropathic pain three groups of medication are generally used: antidepressants (duloxetine, venlafaxine, amitriptyline, nortriptyline), anticonvulsants (gabapentin, pregabalin, carbamazepine) and opioids (such as oxycodone or tramadol). In case of localised pain topical analgesic agents may be considered.

Neuropathic pain medication often gives only partial relief, and may also cause side effects, such as somnolence or dizziness. Dosages need to be increased slowly, and given for at least several weeks in sufficient dosages, before conclusions can be drawn regarding (in)efficacy.