A possible role of the locus coeruleus in complex regional pain syndrome

Peter D. Drummond

doi:10.3389/fnint.2012.00104

Abstract

Heightened sensitivity to painful stimulation commonly spreads from the affected limb to the ipsilateral forehead in patients with complex regional pain syndrome (CRPS). In addition, acoustic startle evokes greater auditory discomfort and increases in limb pain when presented on the affected than unaffected side. In contrast, limb pain ordinarily evokes analgesia in the ipsilateral forehead of healthy participants, and acoustic startle suppresses limb pain. Together, these findings suggest that hemilateral and generalized pain control mechanisms are disrupted in CRPS, and that multisensory integrative processes are compromised. Failure to inhibit nociceptive input from the CRPS-affected limb could sensitize spinal and supraspinal neurons that receive convergent nociceptive and auditory information from hemilateral body sites. Somatosensory, auditory, and emotional inputs may then aggravate pain by feeding into this sensitized nociceptive network. In particular, a disturbance in hemilateral pain processing that involves the locus coeruleus could exacerbate the symptoms of CRPS in some patients.

Highlights

Complex regional pain syndrome (CRPS) usually begins after a fracture, contusion or sprain, but can develop after a minor injury that would normally heal quickly
In the first detailed description of this syndrome, Mitchell (1872) noted that arousal stimuli and emotional distress greatly intensified pain. We recently confirmed this in controlled studies that involved a standard auditory startle stimulus
Patients reported that startle stimuli presented on the CRPSaffected side sounded louder and provoked greater increases in limb pain than contralateral startle stimuli (Knudsen et al, 2011)

Summary

INTEGRATIVE NEUROSCIENCE

Heightened sensitivity to painful stimulation commonly spreads from the affected limb to the ipsilateral forehead in patients with complex regional pain syndrome (CRPS). Acoustic startle evokes greater auditory discomfort and increases in limb pain when presented on the affected than unaffected side. Limb pain ordinarily evokes analgesia in the ipsilateral forehead of healthy participants, and acoustic startle suppresses limb pain. Together, these findings suggest that hemilateral and generalized pain control mechanisms are disrupted in CRPS, and that multisensory integrative processes are compromised. Failure to inhibit nociceptive input from the CRPS-affected limb could sensitize spinal and supraspinal neurons that receive convergent nociceptive and auditory information from hemilateral body sites.

INTRODUCTION

BIDIRECTIONAL INFLUENCES OF SPINAL NORADRENERGIC ACTIVITY ON PAIN