Neuropathic pain treatment
Spinal cord stimulation (SCS) delivered at frequencies and amplitudes transmitting electrical pulses to neural targets below the threshold of perception has been reported as an effective treatment for refractory chronic pain. SCS is a treatment option for severe neuropathic pain not responsive to more conservative treatments 1)
To ascertain the balance between treatment benefits and risks, the French National Authority for Health requested a post-market registry for real-world evaluation of the long-term effectiveness and safety of the therapy.
402 patients undergoing implantation with a Medtronic SCS device as either a primo-implant (n=264) or replacement implant (n=138) were enrolled across 28 representative sites in France. Outcome measures at 2 years included pain intensity, satisfaction with treatment, improvement of pain relief and daily life activity, willingness to undergo the treatment again and use of pain treatments. A patient was considered a responder if, compared to baseline, predominant pain reduction was ≥50%.
At the 2-year follow-up visit, predominant pain intensity for primo-implant patients had decreased from baseline (p<0.001), with responder rates of 55%, 36% and 67% for the lower limbs, back and upper limbs, respectively. Most patients acknowledged an improvement in pain relief (89%) and daily life activity (82%), were satisfied with treatment (91%) and willing to undergo the treatment again (93%). A significant decrease (p<0.01) in the proportion of patients receiving pain treatment was observed for all drug and non-drug treatments. Reported adverse events were in line with literature. Pain intensity at 2 years was comparable for patients in the replacement group, supporting the long-term stability and effectiveness of SCS.
Real world evaluation of the use of spinal cord stimulation under the recommendations of the French Health Authority shows that two years after the first implantation of an SCS device close to 60% of the patients retain a significant pain reduction and 74% show improvement in pain scores [of at least 30%] with significant decreases in drug and non-drug pain treatments 2).
In patients with focal nerve injury and neuropathic pain cutting the nerve to obtain permanent pain reduction can be considered. Surgery is indicated only if a diagnostic nerve block provides temporary pain relief 3).
Current developments are high-frequency stimulation and peripheral nerve field stimulation 4).
Hypoxia and the Na(+)/K(+) ATPase ion transporter may be a novel mechanistic target for the treatment of neuropathic pain. Findings support the possibility of using hypoxia activated pro-drugs to localize treatments for neuropathic pain and nerve injury to injured nerves 5).
Research
Prabhala et al., from the Department of Neuroscience and Experimental Therapeutics, Department of Pathology and Laboratory Medicine, Department of Neurosurgery, Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Acoustic Med Systems, Savoy United States, was to assess the effects of external focused ultrasound on sensory thresholds utilizing a common peroneal nerve injury (CPNI) rat model. CPNI was induced by ligating the common peroneal nerve (CPN) of the left hind paw. Neuropathic phenotype was confirmed using the Von Frey Fibers (VFF) with a 50% mechanical detection threshold below 4.0. The Place Escape Avoidance Paradigm (PEAP) was employed as a behavioral correlate. External FUS treatment was applied to the left L4,5 DRG at 8 W for 3-minutes. There were two treatment groups; one received a single FUS treatment, while the other received two. Control groups consisted of one sham CPNI group that received FUS treatment and a CPNI group that received sham FUS treatment. Behavioral tests were conducted pre-CPNI surgery, 1-week post-surgery, and for 1-week post-FUS treatment(s). CPNI surgery resulted in lower VFF mechanical thresholds in the left hind paw compared to baseline (p < 0.0001) and increased proportion of time spent on bright side compared to baseline values on PEAP (p = 0.0473), indicating neuropathic state. FUS treatment increased VFF thresholds after 24-hours (p < 0.0001), 48-hours (p = 0.0079), and 72-hours (p = 0.0164). VFF returned to baseline values from day 4-7. Following a second FUS treatment on day 8, increased mechanical thresholds were similarly observed after 24-hours (p = 0.0021), 48-hours (p < 0.0001), and 72-hours (p = 0.0256). Control group analysis showed (1) CPNI rats experienced no change in mechanical thresholds following sham FUS treatment and (2) Sham CPNI rats receiving FUS did not experience significantly different mechanical thresholds compared to baseline and post-CPNI values. Post-FUS histological analysis demonstrated healthy ganglion cells without chromatolysis.
The results demonstrate changes in VFF and PEAP in rats who underwent CPNI. Single and multiple doses of external FUS increase mechanical thresholds without inducing histological damage. Based on this results, they demonstrated the potential of FUS to serve as a non-pharmacological and non-ablative neuromodulatory approach for the treatment of allodynia and neuropathic pain 6).
For genetic research to contribute more fully to furthering our knowledge of neuropathic pain, we require an agreed, valid, and feasible approach to phenotyping, to allow collaboration and replication in samples of sufficient size. Results from genetic studies on neuropathic pain have been inconsistent and have met with replication difficulties, in part because of differences in phenotypes used for case ascertainment. Because there is no consensus on the nature of these phenotypes, nor on the methods of collecting them, this study aimed to provide guidelines on collecting and reporting phenotypes in cases and controls for genetic studies. Consensus was achieved through a staged approach: (1) systematic literature review to identify all neuropathic pain phenotypes used in previous genetic studies; (2) Delphi survey to identify the most useful neuropathic pain phenotypes and their validity and feasibility; and (3) meeting of experts to reach consensus on the optimal phenotype(s) to be collected from patients with neuropathic pain for genetic studies. A basic “entry level” set of phenotypes was identified for any genetic study of neuropathic pain. This set identifies cases of “possible” neuropathic pain, and controls, and includes: (1) a validated symptom-based questionnaire to determine whether any pain is likely to be neuropathic; (2) body chart or checklist to identify whether the area of pain distribution is neuroanatomically logical; and (3) details of pain history (intensity, duration, any formal diagnosis). This NeuroPPIC “entry level” set of phenotypes can be expanded by more extensive and specific measures, as determined by scientific requirements and resource availability 7)