Jay Karri,1 Shengai Li,1 Larry Zhang,1 Yen-Ting Chen,1 Argyrios Stampas,1 Sheng Li1,2 1Department of Physical Medicine and Rehabilitation, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; 2TIRR Memorial Hermann Research Center, TIRR Memorial Hermann Hospital, Houston, TX, USA Background: Recent findings have implicated supraspinal origins from the pain neuromatrix–central autonomic network (PNM–CAN) in the generation of neuropathic pain (NP) after spinal cord injury (SCI). The aim of this study was to further investigate the theorized PNM–CAN mechanisms in persons with SCI by using a centrally directed pain intervention, provided by breathing-controlled electrical stimulation (BreEStim), to measure resultant autonomic changes measured by time and frequency domain heart rate variability (HRV) analysis.Methods: Null and active BreEStim interventions were administered to SCI+NP subjects (n=10) in a random order. HRV data and VAS pain scores were collected at resting pre-test and 30 minutes post-test time points. Resting HRV data were also collected from SCI–NP subjects (n=11).Results: SCI+NP subjects demonstrated a lower baseline HRV and parasympathetic tone, via SD of the normal-to-normal intervals (SDNN) and low frequency (LF) parameters, compared with SCI–NP subjects. However, following active BreEStim, SCI+NP subjects exhibited an increase in HRV and parasympathetic tone, most notably via pairs of successive R–R beat lengths varying by greater than 50 ms (NN50) and proportion of NN50 for total number of beats (pNN50) parameters along with lower VAS scores. Additionally, the post-test SCI+NP group was found to have a statistically comparable autonomic profile to the SCI–NP group across all HRV variables, including SDNN and LF parameters.Conclusion: The analgesic effects of active BreEStim in SCI+NP subjects were associated with restoration of autonomic dysfunction in this population. Keywords: autonomic dysfunction, spinal cord injury, neuropathic pain, BreEStim, electrical stimulation, heart rate variability