Successful pain relief in non‐responders to spinal cord stimulation: The combined use of ketamine and spinal cord stimulation

Abstract

Although spinal cord stimulation (SCS) is an established therapy for chronic neuropathic pain, still 30% of patients do not respond adequately to trial stimulation. These so called "non-responders" do not receive a permanent implantation for pain relief. The induction and maintenance of central sensitization plays a pivotal role in (chronic) neuropathic pain and is thought to be the resultant of the activation of the N-methyl-d-aspartate (NMDA) receptor in the dorsal horn. Blocking the NMDA receptor through the use of the non-competitive blocker ketamine has shown to attenuate neuropathic pain, although the undesirable side effects limit its use. The present study was performed to examine whether the combination of SCS with an individually determined sub-effective dose of intrathecal (i.t.) ketamine could convert non-responders into responders in rats with chronic neuropathic pain. Rats received a partial ligation of the sciatic nerve for the induction of neuropathic pain. Animals with tactile hypersensitivity to von Frey monofilaments (n=15) received 30 min of SCS. Non-responders to SCS (n=8) received their individually determined sub-effective i.t. dose of ketamine followed by 30 min of SCS. No side effects of the sub-effective dose of ketamine could be noted. The combined treatment of SCS and sub-effective dose of i.t. ketamine in non-responders resulted in a significant reduction of the withdrawal threshold in all previous non-responders to SCS, thereby converting them into responders to SCS.

Endocannabinoid activation of CB1 receptors contributes to long‐lasting reversal of neuropathic pain by repetitive spinal cord stimulation

“…This incremental efficacy upon repetitive SCS is consistent with, but more marked than, observations in previous reports (Maeda et al, 2008;Yang et al, 2011;Shechter et al, 2013). In our previous work, which used 50 Hz monopolar stimulation over a longer 30 min period (Smits et al, 2006), the acute anti-hyperalgesic effect largely reversed within 1 h. However, when SCS was applied early after pSNL, the effect was longer lasting than in established (16 day) pSNL animals (Truin et al, 2011a). The milder sub-maximal stimulus parameters used here in conjunction with the relatively earlier SCS intervention, 3 days following nerve injury may make it easier to evoke long-lasting and incremental SCSinduced reversal of hyperalgesia.…”

A Continuous Spinal Cord Stimulation Model Attenuates Pain-Related Behavior In Vivo Following Induction of a Peripheral Nerve Injury

“…The results in Figure include animals that were considered responders to SCS, which accounted for 10 out of 16 animals (∼63%) randomized into the SNI + SCS on group. This percentage is congruent with previous reports, which also have discussed criteria to distinguish a responder from a nonresponder . Animals considered SCS responders were those with a paw withdrawal score equivalent to 40% of the average baseline score after 72 hours of stimulation.…”

Spinal Cord Stimulation Reduces Mechanical Hyperalgesia and Glial Cell Activation in Animals with Neuropathic Pain

“…SCS is generally delivered both clinically and in experimental studies below motor threshold [33,38,66,76] and the majority of these use intesnities around 2/3 of motor threshold to produce analgesia [32,89]. The current study showed that intensities at 75% of motor threshold were less effective than 90% and 50% had no effect.…”