Electrical neurostimulation for chronic pain: On selective relay of sensory neural activities in myelinated nerve fibers

Chronic pain affects about 100 million adults in the US. Despite their great need, neuropharmacology and neurostimulation therapies for chronic pain have been associated with suboptimal efficacy and limited long-term success, as their mechanisms of action are unclear. Yet current computational models of pain transmission suffer from several limitations. In particular, dorsal column models do not include the fundamental underlying sensory activity traveling in these nerve fibers. We developed a (simple) simulation test bed of electrical neurostimulation of myelinated nerve fibers with underlying sensory activity. This paper reports our findings so far. Interactions between stimulation-evoked and underlying activities are mainly due to collisions of action potentials and losses of excitability due to the refractory period following an action potential. In addition, intuitively, the reliability of sensory activity decreases as the stimulation frequency increases. This first step opens the door to a better understanding of pain transmission and its modulation by neurostimulation therapies.

[1]  Lee S. Simon RELIEVING PAIN IN AMERICA: A BLUEPRINT FOR TRANSFORMING PREVENTION, CARE, EDUCATION, AND RESEARCH , 2012, Military medicine.

[2]  Ralf Baron,et al.  Neuropathic pain: a clinical perspective. , 2009, Handbook of experimental pharmacology.

[3]  Bengt Linderoth,et al.  Mode of action of spinal cord stimulation in neuropathic pain. , 2006, Journal of pain and symptom management.

[4]  Yun Guan,et al.  Spinal Cord Stimulation: Neurophysiological and Neurochemical Mechanisms of Action , 2012, Current Pain and Headache Reports.

[5]  J. Rubinstein,et al.  Axon termination conditions for electrical stimulation , 1993, IEEE Transactions on Biomedical Engineering.

[6]  Hugh Bostock,et al.  Action potentials and membrane currents in the human node of Ranvier , 1995, Pflügers Archiv.

[7]  Sébastien Joucla,et al.  Modeling extracellular electrical neural stimulation: From basic understanding to MEA-based applications , 2012, Journal of Physiology-Paris.

[8]  Bengt Linderoth,et al.  Spinal cord stimulation: exploration of the physiological basis of a widely used therapy. , 2010, Anesthesiology.

[9]  J. Xing,et al.  Evoked bursting in injured Aβ dorsal root ganglion neurons: A mechanism underlying tactile allodynia , 2012, PAIN.

[10]  J. Holsheimer,et al.  A model of the electrical behaviour of myelinated sensory nerve fibres based on human data , 1999, Medical & Biological Engineering & Computing.

[11]  A. Huxley,et al.  The action potential in the myelinated nerve fibre of Xenopus laevis as computed on the basis of voltage clamp data , 1964, The Journal of physiology.

[12]  William Hollingworth,et al.  Spinal cord stimulation for failed back surgery syndrome: Outcomes in a workers’ compensation setting , 2010, PAIN.

[13]  G. Bennett,et al.  Onset of a painful peripheral neuropathy in rat: a partial and differential deafferentation and spontaneous discharge in A beta and A delta primary afferent neurons. , 1992, Journal of neurophysiology.

[14]  D. Mcneal Analysis of a Model for Excitation of Myelinated Nerve , 1976, IEEE Transactions on Biomedical Engineering.

[15]  L. Simon RELIEVING PAIN IN AMERICA: A BLUEPRINT FOR TRANSFORMING PREVENTION, CARE, EDUCATION, AND RESEARCH , 2012 .

[16]  J. Holsheimer,et al.  Epidural spinal cord stimulation: calculation of field potentials with special reference to dorsal column nerve fibers , 1991, IEEE Transactions on Biomedical Engineering.

[17]  B. Collett,et al.  Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment , 2006, European journal of pain.

[18]  G. Pasternak,et al.  Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. , 2009, The journal of pain : official journal of the American Pain Society.