A review of prospective studies regarding percutaneous peripheral nerve stimulation treatment in the management of chronic pain.

Conventionally, peripheral nerve stimulation (PNS) for treatment of chronic pain has involved a two-stage process: a short-term (e.g., 7 days) trial and, if significant pain relief is achieved, a permanent PNS system is implanted. A percutaneous PNS treatment is now available where a coiled lead may be implanted for up to 60 days with the goal of producing sustained relief. In the present review, published prospective trials using percutaneous PNS treatment were identified and synthesized. The collected evidence indicates that percutaneous PNS treatment for up to 60 days provides durable clinically significant improvements in pain and pain interference. Similar efficacy across diverse targets and etiologies supports the broad applicability for use within the chronic pain population using this nonopioid technology.

What is this review about? This review looks at a drug-free way to treat chronic pain called percutaneous peripheral nerve stimulation (PNS). Percutaneous means it is placed through the skin. PNS applies small amounts of electricity to the nerves to reduce chronic pain. Most PNS systems involve a two-step process. A short trial is first performed to see if a patient has pain relief. A permanent system is then placed if the person had pain relief. Percutaneous PNS treatments are different. They use a thin wire called a lead placed in the body for up to 60 days. The lead is taken out at the end of the treatment period. Studies have shown that this type of PNS treatment can reduce chronic pain even after the treatment is over. No previous article has collected all these studies of percutaneous PNS in one place.What evidence was gathered? This review found evidence from studies on treatment of chronic pain. Pain types included shoulder pain, neuropathic pain and low back pain. It found that percutaneous PNS treatment for up to 60 days can reduce pain and how pain interferes with daily life.How can these data lead to better care for patients? These findings mean that percutaneous PNS treatments could be a useful, non-drug option for many types of chronic pain.

Measuring and modeling the effects of vagus nerve stimulation on heart rate and laryngeal muscles.

BACKGROUND: Reduced heart rate (HR) during vagus nerve stimulation (VNS) is associated with therapy for heart failure, but stimulation frequency and amplitude are limited by patient tolerance. An understanding of physiological responses to parameter adjustments would allow differential control of therapeutic and side effects. To investigate selective modulation of the physiological responses to VNS, we quantified the effects and interactions of parameter selection on two physiological outcomes: one related to therapy (reduced HR) and one related to side effects (laryngeal muscle EMG). METHODS: We applied a broad range of stimulation parameters (mean pulse rates (MPR), intra-burst frequencies, and amplitudes) to the vagus nerve of anesthetized mice. We leveraged the in vivo recordings to parameterize and validate computational models of HR and laryngeal muscle activity across amplitudes and temporal patterns of VNS. We constructed a finite element model of excitation of fibers within the mouse cervical vagus nerve. RESULTS: HR decreased with increased amplitude, increased MPR, and decreased intra-burst frequency. EMG increased with increased MPR. Preferential HR effects over laryngeal EMG effects required combined adjustments of amplitude and MPR. The model of HR responses highlighted contributions of ganglionic filtering to VNS-evoked changes in HR at high stimulation frequencies. Overlap in activation thresholds between small and large modeled fibers was consistent with the overlap in dynamic ranges of related physiological measures (HR and EMG). CONCLUSION: The present study provides insights into physiological responses to VNS required for informed parameter adjustment to modulate selectively therapeutic effects and side effects.

Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice.

BACKGROUND: The vagus nerve is involved in regulating immunity and resolving inflammation. Current strategies aimed at modulating neuroinflammation and cognitive decline, in many cases, are limited and ineffective. OBJECTIVE: We sought to develop a minimally invasive, targeted, vagus nerve stimulation approach (pVNS), and we tested its efficacy with respect to microglial activation and amelioration of cognitive dysfunction following lipopolysaccharide (LPS) endotoxemia in mice. METHODS: We stimulated the cervical vagus nerve in mice using an ultrasound-guided needle electrode under sevoflurane anesthesia. The concentric bipolar needle electrode was percutaneously placed adjacent to the carotid sheath and stimulation was verified in real-time using bradycardia as a biomarker. Activation of vagal fibers was confirmed with immunostaining in relevant brainstem structures, including the dorsal motor nucleus and nucleus tractus solitarius. Efficacy of pVNS was evaluated following administration of LPS and analyses of changes in inflammation and behavior. RESULTS: pVNS enabled stimulation of the vagus nerve as demonstrated by changes in bradycardia and histological evaluation of c-Fos and choline acetyltransferase expression in brainstem nuclei. Following LPS administration, pVNS significantly reduced plasma levels of tumor necrosis factor-α at 3 h post-injection. pVNS prevented LPS-induced hippocampal microglial activation as analyzed by changes in Iba-1 immunoreactivity, including cell body enlargement and shortened ramifications. Cognitive dysfunction following endotoxemia was also restored by pVNS. CONCLUSION: Targeted cervical VNS using this novel percutaneous approach reduced LPS-induced systemic and brain inflammation and significantly improved cognitive responses. These results provide a novel therapeutic approach using bioelectronic medicine to modulate neuro-immune interactions that affect cognition.