Increased efficacy of early spinal cord stimulation in an animal model of neuropathic pain

Abstract

Although spinal cord stimulation (SCS) is an established treatment for chronic neuropathic pain, pain relief is still not successful in a large group of patients. We suggest that the success of SCS may be related to the timing of SCS during the development of chronic neuropathic pain. We therefore compared the effect of SCS applied after 24h of neuropathic pain (early SCS) and after 16days of neuropathic pain (late SCS). For early SCS, male Sprague-Dawley rats (n=13) were implanted with an SCS device, followed by a partial ligation of the sciatic nerve. Using von Frey monofilaments, tactile allodynia was assessed 24h after ligation. Animals with tactile allodynia received 30min of SCS. Withdrawal thresholds were assessed just before SCS, during SCS and until the return to pre-stimulation withdrawal threshold. Results were compared with the data from late SCS (n=29). Out of the 13 allodynic animals that received early SCS, 10 (77%) responded to SCS with significantly increased withdrawal thresholds, compared to 38% in the late SCS group. The increase of the withdrawal threshold in the early SCS group could still be noticed 90min after termination of SCS. In more than half of these animals, pre-stimulation withdrawal thresholds were reached only the next day. Early SCS resulted in an increased number of responders to SCS and furthermore an increased duration of the effect of SCS as compared to late SCS. Early SCS treatment of neuropathic rats is more effective as compared to the late SCS treatment.

Spinal Cord Stimulation Reduces Mechanical Hyperalgesia and Restores Physical Activity Levels in Animals with Noninflammatory Muscle Pain in a Frequency-Dependent Manner

“…The effects of SCS at higher frequencies are similar to that found in animals with nerve injury. 13,14,[18][19][20]22,23,28,67,76 However, our previous studies show that a lower frequency (4 Hz) also reduced nerve injury-induced pain. 67,69,77 The differences between sensitivity to low-and high-frequency SCS between the models is unclear but could relate to different mechanisms of action of low-and high-frequency SCS, since low-frequency (4 Hz) SCS uses μ-opioid receptors and high-frequency (60 Hz) SCS uses δ-opioid receptors.…”

“…Some studies show a cumulative and long-lasting (carryover) effect with repeated SCS, 67,68,81 while others show a more short-term effect that lasts for minutes or hours after SCS. 14,23,69,82,83 It is possible that the differences between studies relates to variables of stimulation. Previous studies have routinely delivered SCS at amplitudes of 60% to 70% of motor threshold, 14,23,83 which is similar to that used clinically.…”

“…14,23,69,82,83 It is possible that the differences between studies relates to variables of stimulation. Previous studies have routinely delivered SCS at amplitudes of 60% to 70% of motor threshold, 14,23,83 which is similar to that used clinically. However, the current study delivered SCS at a higher amplitude, 90% motor threshold.…”

Spinal cord stimulation (scs) improves decreased physical activity induced by nerve injury.

“…This is the first study to show the long-term effectiveness of SCS with repeated treatment and to show improvements in physical activity. Prior studies have shown that a single treatment or treatment for 4 -5 days reduces mechanical hyperalgesia of the paw after nerve injury in multiple models (Guan et al, 2010;Maeda et al, 2009;Smits et al, 2006;Song, Ansah, Meyerson, Pertovaara, & Linderoth, 2013;Truin et al, 2011;Sato et al, 2013;Sato et al, 2014). The magnitude of the reduction varies considerably between studies, with some reports showing nearly complete reversal and others showing a smaller reversal.…”

Ultrasound-Guided Peripheral Nerve Stimulator Placement in Two Soldiers with Acute Battlefield Neuropathic Pain

“…However, in a rat model of neuropathic pain, significant improvements in mechanical allodynia were appreciated in rats that received early SCS. 26 Although neuropathic pain models suggest that central sensitization occurs early after injury via a time-dependent glutamatergic and GABAergic mechanism, proximity of neuromodulatory therapy to the time of injury may be essential for efficacy and possible long-term outcome. 26,27 In our population, young, highly functional soldiers are exposed to unique combat injuries.…”