Deep Brain Stimulation Improves the Symptoms and Sensory Signs of Persistent Central Neuropathic Pain from Spinal Cord Injury: A Case Report

Central neuropathic pain (CNP) is a significant problem after spinal cord injury (SCI). Pharmacological and non-pharmacological approaches may reduce the severity, but relief is rarely substantial. While deep brain stimulation (DBS) has been used to treat various chronic pain types, the technique has rarely been used to attenuate CNP after SCI. Here we present the case of a 54-year-old female with incomplete paraplegia who had severe CNP in the lower limbs and buttock areas since her injury 30 years prior. She was treated with bilateral DBS of the midbrain periaqueductal gray (PAG). The effects of this stimulation on CNP characteristics, severity and pain-related sensory function were evaluated using the International SCI Pain Basic Data Set (ISCIPBDS), Neuropathic Pain Symptom Inventory (NPSI), Multidimensional Pain Inventory and Quantitative Sensory Testing before and periodically after initiation of DBS. After starting DBS treatment, weekly CNP severity ratings rapidly decreased from severe to minimal, paralleled by a substantial reduction in size of the painful area, reduced pain impact and reversal of pain-related neurological abnormalities, i.e., dynamic-mechanical and cold allodynia. She discontinued pain medication on study week 24. The improvement has been consistent. The present study expands on previous findings by providing in-depth assessments of symptoms and signs associated with CNP. The results of this study suggest that activation of endogenous pain inhibitory systems linked to the PAG can eliminate CNP in some people with SCI. More research is needed to better-select appropriate candidates for this type of therapy. We discuss the implications of these findings for understanding the brainstem’s control of chronic pain and for future progress in using analgesic DBS in the central gray

Neurophysiology

Contains research objectives and summary of research.National Institutes of Health (Grant 1 RO1 EY01149-01)National Institutes of Health (Grant 5 P01 GM14940-07)Bell Telephone Laboratories, Inc. (Grant)National Institutes of Health (Grant 5 TO1 GM01555-07)M. I. T. Sloan Fund for Basic Researc

Neurophysiology

Contains research objectives and summary of research on ten research projects.National Institutes of Health (Grant 5 R01 EY01149-02)National Institutes of Health (Grant 1 T01 EY00090-01)Bell Telephone Laboratories, Inc. (Grant)National Institutes of Health (Grant 5 TO1 GM00778-19)National Institutes of Health (Grant 5 TO1 GM01555-08

Neurophysiology

Contains research objectives and summary of research on seventeen research projects and reports on four research projects.National Institutes of Health (Grant 5 TOl EY00090-02)Bell Telephone Laboratories, Inc. (Grant)National Institutes of Health (Grant 5 ROI EY01149-03)National Institutes of Health (Grant NS 12307-01)National Institutes of Health (Grant 1 K04 NS00010

Coincident recording and stimulation of single and multiple neuronal activity with one extracellular microelectrode

This paper describes how an extracellular microelectrode may be used to stimulate neurons with brief, rectangular pulses and afterwards directly record the resultant activity. Two obstacles are the stimulus artifact lingering in the electrical circuitry and transient tip potentials (TTPs) arising from ion depletion at the electrode-tissue interface. Electronic switching between the stimulus source and the recording amplifier eliminates direct stimulus artifact from the electrical circuitry, although high but acceptable switching artifact remains. TTPs revert with time constants that are prominent in the desired recording (0.1–1 ms) and can reach 50 mV when more than 1 μA passes through a typical electrolyte-filled micropipette (for example 2–4 MΩ, filled with 3 M NaCl, and placed in 0.1 M NaCl). They are always negative when cations flow into the tip, they are accompanied by a rise in microelectrode impedance, and they increase as a function of the resting electrode impedance, the duration and amplitude of applied current, and the dilution of the external electrolyte. TTPs were subtracted by differential recording and stimulation through matched micropipettes (one in the brain and one in contiguous electrolyte) and in addition were reduced by pressure ejection of electrolyte. Directly elicited spikes (single or multiple) were detected about 0.5 ms after delivery of a rectangular stimulus pulse in the cerebellar cortex of pentobarbital-anesthetized rats. Typically, 3–4 units could be excited by less than 3 μA cathodal currents at any recording site. All-or-nothing properties, thresholds, and refractoriness to a second pulse within 2–4 ms verified the neuronal nature of the recorded signals. Complex wave forms, probably generated synaptically, were also seen. The technique of coincident extracellular recording and stimulation can be used as a universal search stimulus during microelectrode penetrations through the brain and in determining threshold-distance relations for extracellular stimulation. Where cell penetrations are unstable, it might be usefully substituted for intracellular technique in testing a neuron's behavioral or physiological influences or in exploring a cell membrane's response to drugs (in terms of excitability rather than voltage and impedance)

The membrane potential along an ideal axon in a radial electric field

An equation is developed for the membrane potential expected along a short, closed, straight, unbranched and unmyelinated fiber when a point source of steady current resides in the infinite, uniform, 3-dimensional medium. Most electrode placements induce a membrane potential whose absolute value is greater at terminals than midpoint — between 4.3 and 26.4 times greater in several arbitrary worked examples. Such natural phenomena as the effect of electric fields on the growth of nerve fibers could depend on this heightened susceptibility of terminals to external currents

Spinal CSF from rats with painful peripheral neuropathy evokes catecholamine release from chromaffin cells in vitro

The environment presented by host tissue may influence cellular transplants in the CNS depending on injury or disease. Here we examined whether chronic pain alters cerebrospinal fluid (CSF), thereby enhancing the analgesic effect of transplanted adrenal cells. CSF samples were taken intracisternally from rats with neuropathic pain induced by chronic constriction injury of the sciatic nerve. The samples were applied to cultured bovine chromaffin-cell clusters while catecholamine release was measured by fast cyclic voltammetry. This caused marked and sustained elevations in catecholamine levels, compared to CSF from sham-operated controls, which were reversible by the nicotinic antagonist mecamylamine. These results suggest that chronic neuropathic pain produces increased CSF levels of secretogogues for chromaffin cells, and illustrates the importance of host microenvironmental factors in determining graft function