Neuropathic pain: multiple mechanisms at multiple sites

Abstract

Damage to nerves at various levels of the peripheral and central nervous systems will lead to sensory loss, but in a significant number of patients this is accompanied by a series of distressing painful signs and symptoms. Although animal models and clinical studies have shed much needed light on the underlying mechanisms that produce this maladaptive plasticity, the presently available drugs do not always fully control the pain. This review covers some of the important mechanisms that include ion channels, central processing through excitatory amino acid and neuropeptide receptors and, finally, the role of monoamine systems that originate in the brain and descend to alter spinal events. The targets for presently licensed and potential novel drugs are covered in this context, as are perspectives on future research priorities.

Keywords: :

• allodynia
• antidepressants
• Ca²⁺ channels
• gabapentin
• Na⁺ channels
• neuropathic pain
• NMDA receptors
• noradrenaline
• pregabalin
• serotonin
• substance P

Financial & competing interests disclsoure

The authors acknowledge support from The Wellcome Trust and The London Pain Consortium

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.