Peripheral Neuropathy:Spinal and Supraspinal Contributions to Central Sensitizat

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Neurosignals. 2005;14(4):175-181.

Spinal and Supraspinal Contributions to Central Sensitization in

Peripheral Neuropathy.

Suzuki R, Dickenson A.

Department of Pharmacology, University College London, London, UK.

We will focus on spinal cord dorsal horn lamina I projection

neurones, their supraspinal targets and involvement in pain

processing. These spinal cord neurons respond to tonic peripheral

inputs by wind-up and other intrinsic mechanisms that cause central

hyper-excitability, which in turn can further enhance afferent

inputs. We describe here another hierarchy of excitation - as inputs

arrive in lamina I, neurones rapidly inform the parabrachial area

(PBA) and periaqueductal grey (PAG), areas associated with the

affective and autonomic responses to pain. In addition, PBA can

connect to areas of the brainstem that send descending projections

down to the spinal cord - establishing a loop. The serotonin

receptor, 5HT3, in the spinal cord mediates excitatory descending

inputs from the brainstem. These descending excitatory inputs are

needed for the full coding of polymodal peripheral inputs from spinal

neurons and are enhanced after nerve injury. Furthermore, activity in

this serotonergic system can determine the actions of gabapentin

(GBP) that is widely used in the treatment of neuropathic pain. Thus,

a hierarchy of separate, but interacting excitatory systems exist at

peripheral, spinal and supraspinal sites that all converge on spinal

neurones. The reciprocal relations between pain, fear, anxiety and

autonomic responses are likely to be subserved by these spinal-

brainstem-spinal pathways we describe here. Understanding these pain

pathways is a first step toward elucidating the complex links between

pain and emotions.