Perineural injection of botulinum toxin-A in painful peripheral nerve injury – a case series: pain relief, safety, sensory profile and sample size recommendation

Abstract

Objectives: Subcutaneous injection of botulinum toxin-A (sBONT-A) is a novel treatment for peripheral neuropathic pain. While its analgesic effects are well documented, this treatment is often not comfortable and fails in patients who show signs of sensory loss but rarely allodynia. There are some case reports about perineural BONT-A injection (pBONT-A) which could be an alternative approach. Here we present a retrospective, open label case series of pBONT-A’s efficacy and safety regarding neurological consequences involving changes in somatosensory profiles of both responders and non-responders.

Methods: Sixty patients (53 ± 13years, 77% males) with PNI were treated with pBONT-A after a test injection with a local anesthetic, which prompted distinctive pain relief. Quantitative sensory testing (QST; DFNS protocol) and pain intensity were assessed before and ≥7 days post pBONT-A injection. Definition of response: satisfactory pain reduction of ≥30% NRS (numerical rating scale: 0 = no pain, 10 = worst pain) for ≥4 days.

Statistics: Paired t-test, Mann–Whitney U-test, χ² test.

Results: A temporary weak paresis in one case was clinically verified. The QST -parameters remained unchanged, but patients with more frequent hyperalgesia signs reported less analgesia (p = .04). The pBONT-A injection prompted pain relief by 24.8% (NRS: 6.0 ± 1.7 vs. 4.5 ± 2.1; p < .0001); 57% (n = 34) were responders (NRS: 6.0 ± 1.6 vs. 3.4 ± 1.6, relief of 43.4%; p < .0001). Based on these results, we suggest that future parallel design trials on pBONT-A need to include at least 84 patients.

Discussion: Ultrasound-guided pBONT-A injection seems to be a safe treatment leading to a sufficient pain relief for some months without sensory changes. Surprisingly, pBONT-A showed a pronounced analgesic effect also in patients without signs of hyperalgesia.

Keywords:

• Botulinum toxin-A
• peripheral nerve injury
• perineural
• quantitative sensory testing
• neuropathic pain

Note

Transparency

Declaration of funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Author contributions

All authors meet all four criteria for authorship recommended by ICMJE. All authors have seen and agree with the final contents of the manuscript. Ethical proposal: L.B.E., M.K., C.M. Study design and conception: C.M., C.A.A.G. Injections: C.A.A.G., C.M. Statistics and analysis: C.H.M.F., M.K., J.V., C.M. Manuscript: C.H.M.F., L.B.E., M.K., C.M., J.V., A.W., P.K.Z., C.A.A.G. Data interpretation: C.H.M.F., M.K., J.V., C.M., L.B.E. Responsibility for concept: C.M., P.K.Z.

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors are indebted to the patients for their consent and cooperation who agreed in using clinical data for this publication. The authors would also like to thank the editorial board of Current Medical Research and Opinion for review and criticism in improving the manuscript.

Prior presentation: Preliminary data of this study were presented as a poster presentation at the Congress of the German section of the International Association for the Study of Pain Schmerzkongress; 2017 Oct 11–14; Mannheim, Germany. An oral presentation was given at the NEUPSIG International Congress on Neuropathic pain; 2017 Jun 15–18; Gothenburg, Sweden.

Notes

1 Botox is a registered trade name of Allergan Pharmaceuticals, Ireland