Progress in Sympathetically Mediated Pathological Pain

Abstract

Aim of review Many chronic pain conditions remain difficult to treat, presenting a high burden to society. Conditions such as complex regional pain syndrome may be maintained or exacerbated by sympathetic activity. Understanding the interactions between sympathetic nervous system and sensory system will help to improve the effective management of pathological pain including intractable neuropathic pain and persistent inflammatory pain. Method We first described the discovery of abnormal connections between sympathetic and sensory neurons. Subsequently, the functional roles of sympathetic sprouting in altered neuronal excitability and increased pain sensitivity were discussed. The mechanisms of the sympathetic sprouting were focusing on its relationship with neurotrophins, local inflammation, and abnormal spontaneous activity. Finally, we discussed clinical implications and conflicting findings in the laboratory and clinical research with respect to the interaction between sympathetic system and sensory system. Recent findings The findings that sprouting of sympathetic fibers into the sensory ganglia (dorsal root ganglion) after peripheral nerve injury, offers a possible explanation of the sympathetic involvement in pain. It is also suggested that releases of adenosine triphosphate (ATP), in addition to norepinephrine, from sympathetic nerve endings play important roles in sympathetic-mediated pain. New evidence indicates the importance of sympathetic innervation in local inflammatory responses. Summary Hopefully, this review will reinvigorate the study of sympathetic-sensory interactions in chronic pain conditions, and help to better understand how sympathetic system contributes to this serious clinical problem.

Interventional Radiofrequency Treatment for the Sympathetic Nervous System: A Review Article

“…Furthermore, the studies included in this review were limited to those describing RF treatments of the following sympathetic targets applied in clinical practice [7,8]: sphenopalatine ganglion, stellate ganglion, cervical, thoracic, or lumbar sympathetic ganglia, celiac plexus, splanchnic nerves, superior hypogastric plexus, and ganglion impar. Of note, it is possible that sympathetic activity may play a role outside these SNS sites, such as in the dorsal root ganglia as well as sinuvertebral and basivertebral nerves, but the pathophysiology is not well understood and it was therefore not included in this study [9,[20][21][22].…”

“…SNS-driven pain signaling can be dampened via neural blockade of key sympathetic nerves or ganglia. Pain relieved by SNS blockage is said to be SMP [2,9], whereas pain not relieved by SNS blockage is considered sympathetically independent pain (SIP) [2,9]. Typically, temporary nerve blocks are used with diagnostic intent to distinguish between these clinical features before neurolytic measures are pursued [10][11][12].…”

The Delayed-Onset Mechanical Pain Behavior Induced by Infant Peripheral Nerve Injury Is Accompanied by Sympathetic Sprouting in the Dorsal Root Ganglion

“…Aberrant sprouting of sympathetic fibers around neuron somas at dorsal root ganglia (DRG) after peripheral nerve injury has been demonstrated to be correlated with adult neuropathic pain behaviors [13][14][15][16][17][18][19][20]. The sympathetic sprouting fibers may increase the expression of α-adrenergic receptors, enhance excitability, produce spontaneous activity, and alter the microenvironment of DRG neurons [21][22][23][24][25][26]. Surgical sympathectomy can alleviate mechanical allodynia induced by spinal nerve lesions [27].…”

Unclear etiology and current hypotheses of the pathogenesis of fibromyalgia

“…Chronic sympathetic hyperactivity results in alterations in dorsal root ganglia, such as new abnormal connections between the sympathetic and nociceptive system [11]. Chronic sympathetic hyperactivity and neuroplasticity in dorsal root ganglia are the basis of sympathetically maintained pain concept [29]. These phenomena explain not only pain in fibromyalgia, but the other symptoms too, such as anxiety or sleep disturbances.…”