The Effect of Electrical and Mechanical Stimulation on the Regenerating Rodent Facial Nerve

Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
The Laryngoscope (Impact Factor: 2.14). 03/2010; 120(6):1094-102. DOI: 10.1002/lary.20903
Source: PubMed


Investigators have long sought realistic methods to accelerate regeneration following nerve injury. Herein, we investigated the degree to which manual target muscle manipulation and brief electrical stimulation of the facial nerve, alone or in combination, affects recovery following rat facial nerve injury.
Prospective, randomized animal study.
Sixty rats were randomized to three groups: brief electrical stimulation (BES), mechanical stimulation of the whisker pad (MEC), or both (COMBO). Animals underwent facial nerve transection and immediate microsurgical repair. In BES and COMBO groups, transection was preceded by 1-hour (3 V, 20 Hz square wave) electrical stimulation. Animals were tested weekly, with 5-minute recording sessions of whisker movement. In the MEC and COMBO groups, animals received 5 minutes of daily massage to the left whisker pad throughout the recovery period. Whisking behavior was analyzed for comparisons.
The BES and MEC groups demonstrated improved functional recovery in all whisking parameters compared with the COMBO group or historical controls at most time points between postoperative weeks 1 and 7. After 12 weeks, functional recovery remained superior in the BES and MEC groups compared with the COMBO and control groups, although the effect was no longer statistically significant.
We observed an accelerative recovery effect of either electrical nerve stimulation or massage of the whisker pad on whisking behavior. The combination of both interventions had a negating effect on the acceleration of recovery. The potential clinical utility of these modalities bears consideration, and their negating interaction warrants further study.

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    • "Vibrissal piloerector muscles are innervated only by the buccal branch of the facial nerve (Dorfl 1985). As previously shown, video-based motion analysis is non-invasive and allows vibrissal movements to be precisely quantified (Carvell and Simons 1990; Guntinas-Lichius et al. 2005; Hadlock et al. 2010). Under light anesthesia, all vibrissae on each side of the face were clipped except for the two large vibrissae in row C (see Fig. 1 in Arvidsson 1982). "
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    ABSTRACT: We have recently shown that manual stimulation of target muscles promotes functional recovery after transection and surgical repair to pure motor nerves (facial: whisking and blink reflex; hypoglossal: tongue position). However, following facial nerve repair, manual stimulation is detrimental if sensory afferent input is eliminated by, e.g., infraorbital nerve extirpation. To further understand the interplay between sensory input and motor recovery, we performed simultaneous cut-and-suture lesions on both the facial and the infraorbital nerves and examined whether stimulation of the sensory afferents from the vibrissae by a forced use would improve motor recovery. The efficacy of 3 treatment paradigms was assessed: removal of the contralateral vibrissae to ensure a maximal use of the ipsilateral ones (vibrissal stimulation; Group 2), manual stimulation of the ipsilateral vibrissal muscles (Group 3), and vibrissal stimulation followed by manual stimulation (Group 4). Data were compared to controls which underwent surgery but did not receive any treatment (Group 1). Four months after surgery, all three treatments significantly improved the amplitude of vibrissal whisking to 30° versus 11° in the controls of Group 1. The three treatments also reduced the degree of polyneuronal innervation of target muscle fibers to 37% versus 58% in Group 1. These findings indicate that forced vibrissal use and manual stimulation, either alone or sequentially, reduce target muscle polyinnervation and improve recovery of whisking function when both the sensory and the motor components of the trigemino-facial system regenerate.
    Experimental Brain Research 07/2011; 212(1):65-79. DOI:10.1007/s00221-011-2697-9 · 2.04 Impact Factor
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    • "With respect to functional improvements, we have recently shown that, after facial nerve injury, manual stimulation (MS) of denervated whisker pads reduces the proportion of polyinnervated neuro-muscular junctions (NMJs). Furthermore, the shift towards the normal monoinnervated state is associated with improved whisking function and blink reflexes (Angelov et al., 2007; Bischoff et al., 2009; Hadlock et al., 2010a). Interestingly , a number of key growth factors appear to be required during MS to both decrease polyinnervation and improve whisking function. "
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    ABSTRACT: Functional recovery following facial nerve injury is poor. Adjacent neuromuscular junctions (NMJs) are "bridged" by terminal Schwann cells and numerous regenerating axonal sprouts. We have recently shown that manual stimulation (MS) restores whisking function and reduces polyinnervation of NMJs. Furthermore, MS requires both insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF). Here, we investigated whether fibroblast growth factor-2 (FGF-2) was also required for the beneficial effects of MS. Following transection and suture of the facial nerve (facial-facial anastomisis, FFA) in homozygous mice lacking FGF-2 (FGF-2(-/-)), vibrissal motor performance and the percentage of poly-innervated NMJ were quantified. In intact FGF-2(-/-) mice and their wildtype (WT) counterparts, there were no differences in amplitude of vibrissal whisking (about 50°) or in the percentage of polyinnervated NMJ (0%). After 2 months FFA and handling alone (i.e. no MS), the amplitude of vibrissal whisking in WT-mice decreased to 22±3°. In the FGF-2(-/-) mice, the amplitude was reduced further to 15±4°, that is, function was significantly poorer. Functional deficits were mirrored by increased polyinnervation of NMJ in WT mice (40.33±2.16%) with polyinnervation being increased further in FGF-2(-/-) mice (50.33±4.33%). However, regardless of the genotype, MS increased vibrissal whisking amplitude (WT: 33.9°±7.7; FGF-2(-/-): 33.4°±8.1) and concomitantly reduced polyinnervation (WT: 33.9%±7.7; FGF-2(-/-): 33.4%±8.1) to a similar extent. We conclude that, whereas lack of FGF-2 leads to poor functional recovery and target reinnervation, MS can nevertheless confer some functional benefit in its absence.
    Neuroscience 03/2011; 182:241-7. DOI:10.1016/j.neuroscience.2011.03.032 · 3.36 Impact Factor
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    • "Hadlock and co-workers investigated the effects of a local brief electrical stimulation (1 h, 3 V, 20 Hz square wave), a mechanical (manual) target muscle manipulation, or both on functional recovery (whisker movement) of transected and repaired facial nerve of rats [92]. Either therapy alone led to long last better effects than that of untreated rats or animals submitted to an association of the two methods. "
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    ABSTRACT: The etiology of Bell's palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system. Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg-1). Animals were sacrificed seven days later. Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction. FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell's palsy.
    Journal of Brachial Plexus and Peripheral Nerve Injury 11/2010; 5(01):16. DOI:10.1186/1749-7221-5-16
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