External focused ultrasound treatment for neuropathic pain induced by common peroneal nerve injury

Abstract INTRODUCTION Various rodent models have long been employed to study treatments for chronic pain. However, these studies have resulted in unsuccessful phase-I and II human trials that have failed to result in viable options for patients. Though limitations of animal models are no doubt one issue, lack of objective markers corresponding with pain relief play a role. Our lab has shown significant pain relief in a common peroneal nerve injury (CPNI) rat model following administration of external pulsed low-intensity focused ultrasound (liFUS), thus, establishing external liFUS as a promising technique for treatment of neuropathic pain. Current knowledge of liFUS effects are limited to observable behavioral changes, and little is known of the mechanism of action. To successfully translate this device into the clinic, we examine molecular changes in the inflammatory cascade. METHODS Male rats underwent CPNI to induce neuropathic pain. External liFUS treatment was performed on the L5 dorsal root ganglion (DRG) in the neuropathic model, which was determined from responses to Von Frey fibers (VFF). 24 h post liFUS treatment, L5 DRGs were obtained from 4 distinct cohorts: rats that underwent CPNI with liFUS, CPNI with sham liFUS, sham CPNI with liFUS, and sham CPNI sham liFUS (n = 4 for each group). Using a membrane-based sandwich immunoassay (Proteome Profiler Rat Cytokine Array Kit from R&D System), we assessed relative abundances of 6 anti-inflammatory cytokines and 16 pro-inflammatory cytokines. RESULTS CPNI resulted in an 82.5% decrease of tumor necrosis factor alpha (TNFa) and a 61.8% increase of macrophage inflammatory protein 1-alpha (MIP-1a). liFUS led to a 60% decrease in MIP-1a and a 40% increase in TNFa. Other changes in cytokines were not affected by CPNI or liFUS. CONCLUSION liFUS resulted in similar changes in TNFa and MIP-1a, as compared to spinal cord stimulation and other medical treatments for pain syndromes. Further work will examine inflammatory responses over time and in female rats.

Download Full-text

Low Intensity Focused Ultrasound Increases Duration of Anti‐Nociceptive Responses in Female Common Peroneal Nerve Injury Rats

Neuromodulation Technology at the Neural Interface ◽

10.1111/ner.13531 ◽

2021 ◽

Author(s):

Andrea Liss ◽

Abigail Hellman ◽

Vraj J. Patel ◽

Teresa Maietta ◽

Kanakaharini Byraju ◽

...

Keyword(s):

Nerve Injury ◽

Peroneal Nerve ◽

Focused Ultrasound ◽

Common Peroneal Nerve ◽

Low Intensity ◽

Nociceptive Responses ◽

Peroneal Nerve Injury

Download Full-text

Development of a common peroneal nerve injury model in domestic swine for the study of translational neuropathic pain treatments

Journal of Neurosurgery ◽

10.3171/2020.9.jns202961 ◽

2021 ◽

pp. 1-8

Author(s):

Abigail Hellman ◽

Teresa Maietta ◽

Alicia Clum ◽

Kanakaharini Byraju ◽

Nataly Raviv ◽

...

Keyword(s):

Neuropathic Pain ◽

Nerve Injury ◽

Peroneal Nerve ◽

Common Peroneal Nerve ◽

Pain Behavior ◽

Swine Model ◽

Pain Model ◽

Neuropathic Pain Model ◽

Peroneal Nerve Injury ◽

Domestic Swine

OBJECTIVE To date, muscular and bone pain have been studied in domestic swine models, but the only neuropathic pain model described in swine is a mixed neuritis model. Common peroneal nerve injury (CPNI) neuropathic pain models have been utilized in both mice and rats. METHODS The authors developed a swine surgical CPNI model of neuropathic pain. Behavioral outcomes were validated with von Frey filament testing, thermal sensitivity assessments, and social and motor scoring. Demyelination of the nerve was confirmed through standard histological assessment. The contralateral nerve served as the control. RESULTS CPNI induced mechanical and thermal allodynia (p < 0.001 [n = 10] and p < 0.05 [n = 4], respectively) and increased pain behavior, i.e., guarding of the painful leg (n = 12). Myelin protein zero (P0) staining revealed demyelination of the ligated nerve upstream of the ligation site. CONCLUSIONS In a neuropathic pain model in domestic swine, the authors demonstrated that CPNI induces demyelination of the common peroneal nerve, which the authors hypothesize is responsible for the resulting allodynic pain behavior. As the anatomical features of domestic swine resemble those of humans more closely than previously used rat and mouse models, utilizing this swine model, which is to the authors’ knowledge the first of its kind, will aid in the translation of experimental treatments to clinical trials.

Download Full-text

Effects of external low intensity focused ultrasound on electrophysiological changes in vivo in a rodent model of common peroneal nerve injury

Neuroscience ◽

10.1016/j.neuroscience.2020.01.016 ◽

2020 ◽

Vol 429 ◽

pp. 264-272 ◽

Cited By ~ 1

Author(s):

Abigail Hellman ◽

Teresa Maietta ◽

Kanakaharini Byraju ◽

Yunseo Linda Park ◽

Andrea Liss ◽

...

Keyword(s):

Nerve Injury ◽

Peroneal Nerve ◽

Focused Ultrasound ◽

Common Peroneal Nerve ◽

Rodent Model ◽

Low Intensity ◽

Peroneal Nerve Injury

Download Full-text

Isokinetic cross-training effect in foot drop following common peroneal nerve injury

Isokinetics and Exercise Science ◽

10.3233/ies-140559 ◽

2015 ◽

Vol 23 (1) ◽

pp. 17-20 ◽

Cited By ~ 4

Author(s):

Andrea Manca ◽

Francesco Pisanu ◽

Enzo Ortu ◽

Edoardo De Natale ◽

Francesca Ginatempo ◽

...

Keyword(s):

Nerve Injury ◽

Peroneal Nerve ◽

Common Peroneal Nerve ◽

Foot Drop ◽

Training Effect ◽

Cross Training ◽

Peroneal Nerve Injury

Download Full-text

Iatrogenic common peroneal nerve injury during harvesting of semitendinosus tendon for anterior cruciate ligament reconstruction

BMJ Case Reports ◽

10.1136/bcr-2020-240736 ◽

2021 ◽

Vol 14 (4) ◽

pp. e240736

Author(s):

Raf Mens ◽

Albert van Houten ◽

Roy Bernardus Gerardus Brokelman ◽

Roy Hoogeslag

Keyword(s):

Anterior Cruciate Ligament ◽

Nerve Injury ◽

Peroneal Nerve ◽

Cruciate Ligament ◽

Common Peroneal Nerve ◽

Peroneal Nerve Injury ◽

The Common ◽

Anterior Cruciate ◽

Incision Technique

We present a case of iatrogenic injury to the common peroneal nerve (CPN) occurring due to harvesting of a hamstring graft, using a posterior mini-incision technique. A twitch of the foot was noted on retraction of the tendon stripper. After clinically diagnosing a CPN palsy proximal to the knee, the patient was referred to a neurosurgeon within 24 hours. An electromyography (EMG) was not obtained since it cannot accurately differentiate between partial and complete nerve injury in the first week after injury. Because the nerve might have been transacted by the tendon stripper, surgical exploration within 72 hours after injury was indicated. An intraneural haematoma was found and neurolysis was performed to decompress the nerve. Functioning of the anterior cruciate ligament was satisfactory during follow-up. Complete return of motor function of the CPN was observed at 1-year follow-up, with some remaining hypoaesthesia.

Download Full-text