Treatment of Neuropathic Pain: Old Concepts and Novel Advances

The medical management of neuropathic pain consists of five main classes of oral medication (serotonin/norepinephrine re-uptake blockers, Na-blocker anticonvulsants, Ca-blocker anticonvulsants, tramadol and opioids) and several categories of topical medications for patients with cutaneous allodynia and hyperalgesia (capsaicin and local anaesthetics). In many cases an early combination of compounds affecting different mechanisms is useful. Antidepressants: The effectiveness of tricyclic antidepressants (TCAs) in neuropathic pain may account for their broad range of pharmacological actions. In a recent controlled trial of venlafaxine hydrochloride, which blocks both serotonin and norepinephrine re-uptake, and imipramine hydrochloride in patients with painful polyneuropathy, both antidepressants demonstrated superior pain relief compared with placebo but did not differ from each other. Anticonvulsants (Ca-channel blockers): For pregabalin, a new anticonvulsant, current controlled clinical trials show efficacy for postherpetic neuralgia (PHN) and diabetic painful neuropathy (DPN). Its mechanism is an action on the a2d-subunit of neuronal calcium channels which are involved in the allodynic response in animal models of neuropathic pain. The adverse effects include somnolence and dizziness and mild peripheral edema, especially during the early treatment phase. However, its generally excellent tolerability, safety, and lack of drug interactions and negative impact on cardiac function distinguish pregabalin from most other oral medications used for the treatment of chronic neuropathic pain. An advantage is its superior bioavailability which makes it easier to use without the need of long titration periods. Anticonvulsants (Na-channel blockers): For lamotrigine there is evidence of efficacy in HIV sensory neuropathy, DPN, and central poststroke pain as well as in a subgroup of patients with incomplete spinal cord lesions. Carbamazepine is very effective in trigeminal neuralgia. However, the strength of evidence is much lower for the benefit of these drugs in other types of neuropathic pain. Long-acting opioids: Several recent controlled trials have clearly demonstrated sustained efficacy of opioids in neuropathic pain states. Topical lidocaine: A second topical medication for neuropathic pain are local anaesthetics. Local anaesthetics block voltage-dependent sodium channels.