A digital wireless system for closed-loop inhibition of nociceptive signals

Neurostimulation of the spinal cord or brain has been used to inhibit nociceptive signals in pain management applications. Nevertheless, most of the current neurostimulation models are based on open-loop system designs. There is a lack of closed-loop systems for neurostimulation in research with small freely-moving animals and in future clinical applications. Based on our previously developed analog wireless system for closed-loop neurostimulation, a digital wireless system with real-time feedback between recorder and stimulator modules has been developed to achieve multi-channel communication. The wireless system includes a wearable recording module, a wearable stimulation module and a transceiver connected to a computer for real-time and off-line data processing, display and storage. To validate our system, wide dynamic range neurons in the spinal cord dorsal horn have been recorded from anesthetized rats in response to graded mechanical stimuli (brush, pressure and pinch) applied in the hind paw. The identified nociceptive signals were used to automatically trigger electrical stimulation at the periaqueductal gray in real time to inhibit their own activities by the closed-loop design. Our digital wireless closed-loop system has provided a simplified and efficient method for further study of pain processing in freely-moving animals and potential clinical application in patients.

[1]  Sooyoung Yoo,et al.  MobileMed: A PDA-Based Mobile Clinical Information System , 2006, IEEE Transactions on Information Technology in Biomedicine.

[2]  M. Bushnell,et al.  Pain affect encoded in human anterior cingulate but not somatosensory cortex. , 1997, Science.

[3]  Steve M. Potter,et al.  Closed-Loop, Open-Source Electrophysiology , 2010, Front. Neurosci..

[4]  Jingyu Chang,et al.  Brain Stimulation for Neurological and Psychiatric Disorders, Current Status and Future Direction , 2004, Journal of Pharmacology and Experimental Therapeutics.

[5]  Michael K. Nicholas,et al.  The contribution of psychosocial factors to the development of chronic pain: The key to better outcomes for patients? , 2007, Pain.

[6]  Qing Lin,et al.  Effects of GABA and glycine receptor antagonists on the activity and PAG-induced inhibition of rat dorsal horn neurons , 1996, Brain Research.

[7]  G. Pellegrino,et al.  Vicarious responses to pain in anterior cingulate cortex: Is empathy a multisensory issue? , 2004, Cognitive, affective & behavioral neuroscience.

[8]  Euisik Yoon,et al.  BioBolt: A minimally-invasive neural interface for wireless epidural recording by intra-skin communication , 2011, 2011 Symposium on VLSI Circuits - Digest of Technical Papers.

[9]  M. Millan,et al.  The induction of pain: an integrative review , 1999, Progress in Neurobiology.

[10]  Maysam Ghovanloo,et al.  A low-noise clockless simultaneous 32-channel wireless neural recording system with adjustable resolution , 2011 .

[11]  Geert Crombez,et al.  Pain-related fear is more disabling than pain itself: evidence on the role of pain-related fear in chronic back pain disability , 1999, Pain.

[12]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[13]  M. Zimmermann,et al.  Ethical guidelines for investigations of experimental pain in conscious animals , 1983, Pain.

[14]  M. Millan.  Descending control of pain , 2002, Progress in Neurobiology.

[15]  Qi Xu,et al.  A fully implanted programmable stimulator based on wireless communication for epidural spinal cord stimulation in rats , 2012, Journal of Neuroscience Methods.

[16]  M. Kringelbach,et al.  Translational principles of deep brain stimulation , 2007, Nature Reviews Neuroscience.

[17]  F. Blyth,et al.  Chronic pain in Australia: a prevalence study , 2001, Pain.

[18]  J. Stamford.  Descending control of pain. , 1995, British journal of anaesthesia.

[19]  Thermpon Ativanichayaphong,et al.  A combined wireless neural stimulating and recording system for study of pain processing , 2008, Journal of Neuroscience Methods.

[20]  Peter Croft,et al.  Social risks for disabling pain in older people: A prospective study of individual and area characteristics , 2008, PAIN®.

[21]  S. Martinoia,et al.  A general-purpose system for long-term recording from a microelectrode array coupled to excitable cells , 1993, Journal of Neuroscience Methods.

[22]  J. E. Wells,et al.  Epidemiology of pain in New Zealand , 1991, Pain.

[23]  Khosrow Behbehani,et al.  Recognition and inhibition of dorsal horn nociceptive signals within a closed-loop system , 2010, 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology.

[24]  U. Lindblom,et al.  Motor cortex stimulation as treatment of trigeminal neuropathic pain. , 1993, Acta neurochirurgica. Supplementum.

[25]  Khalil Najafi,et al.  A low-power, low-voltage, user-programmable, wireless interface for reliable neural recording , 2011, 2011 IEEE Biomedical Circuits and Systems Conference (BioCAS).

[26]  J. Hildebrand,et al.  Multi-unit recordings reveal context-dependent modulation of synchrony in odor-specific neural ensembles , 2000, Nature Neuroscience.

[27]  A. Grace,et al.  Intracellular and extracellular electrophysiology of nigral dopaminergic neurons—2. Action potential generating mechanisms and morphological correlates , 1983, Neuroscience.

[28]  P. Mäntyselkä,et al.  Pain as a reason to visit the doctor: a study in Finnish primary health care , 2001, Pain.

[29]  Tzung K Hsiai,et al.  Flexible microelectrode arrays to interface epicardial electrical signals with intracardial calcium transients in zebrafish hearts , 2012, Biomedical microdevices.

[30]  Fu-Shan Jaw,et al.  Miniature telemetry system for the recording of action and field potentials , 2005, Journal of Neuroscience Methods.

[31]  M. Zimmermann,et al.  Epidemiology of pain , 1990, Pain.

[32]  Patrick D Wolf,et al.  A single-chip signal processing and telemetry engine for an implantable 96-channel neural data acquisition system , 2007, Journal of neural engineering.

[33]  W D Willis,et al.  The role of 5-HT3 receptors in periaqueductal gray-induced inhibition of nociceptive dorsal horn neurons in rats. , 1996, The Journal of pharmacology and experimental therapeutics.

[34]  D. Price,et al.  Central neural mechanisms that interrelate sensory and affective dimensions of pain. , 2002, Molecular interventions.

[35]  Michael J. Cousins,et al.  Chronic pain and frequent use of health care , 2004, Pain.

[36]  Yong Yu,et al.  A real-time data acquisition system for mechanical nanometer displacement sensors , 2011, 2011 IEEE International Conference on Automation and Logistics (ICAL).

[37]  T Hirayama,et al.  Chronic motor cortex stimulation in patients with thalamic pain. , 1993, Journal of neurosurgery.

[38]  Naoshige Uchida,et al.  A wireless multi-channel neural amplifier for freely moving animals , 2011, Nature Neuroscience.

[39]  J. Farrar,et al.  Core outcome measures for chronic pain clinical trials: IMMPACT recommendations , 2003, Pain.

[40]  D. Bahr,et al.  Characterization of flexible ECoG electrode arrays for chronic recording in awake rats , 2008, Journal of Neuroscience Methods.

[41]  Damien Lapray,et al.  A novel miniature telemetric system for recording EEG activity in freely moving rats , 2008, Journal of Neuroscience Methods.

[42]  J. Farrar,et al.  Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale , 2001, PAIN.

[43]  M. Kuppermann,et al.  Chronic Pelvic Pain: Prevalence, Health‐Related Quality of Life, and Economic Correlates , 1996, Obstetrics and gynecology.

[44]  M. Bushnell,et al.  Pain perception: is there a role for primary somatosensory cortex? , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Panos Barlas,et al.  Effects of TENS frequency, intensity and stimulation site parameter manipulation on pressure pain thresholds in healthy human subjects , 2003, Pain.

[46]  D. V. Reynolds,et al.  Surgery in the Rat during Electrical Analgesia Induced by Focal Brain Stimulation , 1969, Science.