New Drug Shows Promise For Treating Chronic Neuropathic Pain

New Treatment For Neuropathy 2022:

Finally, more genetic forms of polyneuropathy are being discovered, and novel treatments have become available for disorders such as familial transthyretin amyloidosis. Thus, genetic testing could be also considered, although the role of routine genetic testing remains unclear. Two key strategies that developed from spinal opioid gene therapy have proven to be efficacious to induce analgesia in neuropathy in preclinical models. Glorioso and Fink described a novel approach for attenuating pain without the induction of tolerance or systemic side effects by the intradermal inoculation of an HSV vector delivering pain-modulating transgenes to sensory neurons in vivo along with standard pain treatments [148]. The other approach based on opioid delivery included the administration of opioid receptor encoding genes [149].

Nine types of sodium channels have been identified that have a similar overall structure with a few minor differences in the sequence of amino acids (Nav1.1 to Nav1.9) [158]. Among these, subtypes Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9 were found to have a role in nociception, because they were upregulated in several pain models [157]. Transcutaneous electrical nerve stimulation (TENS) is an expensive, non-invasive, self-adhesive to relieve pain in CNP, PNP, complex regional pain syndrome, phantom limb pain, and fibromyalgia [75]. Consensus statement for the management of chronic neuropathic pain by the Canadian Pain Society.

It advocates a personalized care approach to ultimately reduce sequelae and the related health care burden and optimize quality of life for people with diabetes and DPN. Microneurography may serve as a biomarker for the irritable nociceptor phenotype and as an objective, quantifiable measure of subjective pain68. In this technique, a microelectrode is inserted into the nerve fascicle and records action potentials from a single axon, thus measuring the degree of spontaneous activity from the peripheral nerve. Patients with painful polyneuropathy demonstrate a higher proportion of spontaneously active or mechanically sensitized C-nociceptors in contrast to patients with painless polyneuropathy and also showed less activity-dependent slowing suggestive of a peripheral sensitization69.

SCS, in which stimulating electrodes are surgically implanted in the epidural space, is extensively used for pain reduction in failed back surgery syndrome and has been compared in clinical trials against best medical care (but not sham procedures) for treatment of painful DPN (145). These trials found large effect sizes favoring pain reduction with SCS over a 6-month follow-up period. In longitudinal follow-up from a multicenter RCT of SCS, about one-third of recipients reported at least a 50% reduction in pain compared to baseline at 60 months (146). In DPN, spontaneous ephaptic transmission from metabolically injured peripheral sensory afferent fibers generates sensation of neuropathic pain that often develops a chronic quality through central spinal sensitization. Various modes of intermittent electrical stimulation have been trialed to interrupt pain sensation.

Serum NfL levels have also been shown to correlate with treatment response in patients with hereditary transthyretin amyloid (variant transthyretin amyloidosis, or ATTRv) polyneuropathy30. While nonspecific, this correlation with treatment response suggests that NfL holds promise as a biomarker for disease progression and treatment response in neurodegenerative diseases, including DPN. It is a well-established fact that navigate to these guys the process of pain transmission and signaling depends upon ion channels, which can thus be considered a primary target in treating conditions such as chronic neuropathic pain. Voltage-gated channels or leak channels could regulate the resting membrane potential [157,158]. Damage, nerve lesion, or inflammation could result in hyper-responsiveness of the ion channels, thus leading to unregulated neuronal firing [159].

Clinically, a formal exercise prescription can stress the therapeutic value of exercise, encourage increased activity, and regulate progression to allow tissue adaptation without causing injury. Exercise prescriptions for individuals with DPN should include information on exercise type, mode, goal intensity, frequency, and duration (Table 3). Participation in weight-bearing exercise in individuals without severe foot deformity or peripheral vascular disease has great post to read been found to be safe. Individuals with DPN should seek medical clearance for cardiovascular risk before starting a formal exercise program. The usual dose is 600 mg daily, but higher doses (600 mg twice or three times daily) may occasionally be useful if symptom relief is only partial (=30% reduction). The duration of RCTs using ALA in symptomatic DPN has been limited to =6 months, similar to those using analgesic drugs in painful DPN, which lasted =3 months.

In a recent study, it was also found that four continuous rTMS sessions can recover refractory central neuropathic pain over three weeks by applying electromagnetic induction of 20 Hz on the primary motor cortex [103]. Therefore, TMS could represent an incredible alternative for treating neuropathic pain. Certain TMS findings will be helpful in the early diagnoses and prognostic predictions of multiple sclerosis, psychogenic paresis, plexus neuropathy, stroke, and cervical spondylosis [104,105,106]. However, rTMS is contraindicated in patients with deep brain electrodes, aneurysm clips, cochlear implants, cardiac pacemakers, and an epilepsy history [2].

The drug’s efficacy was supported by the results of two 12-week, double-blind, randomized, dose-controlled multicenter clinical trials. In the first study, 29% ‘ 2% of the treatment group demonstrated a =50% reduction in average pain at the primary assessment during week 8 [19, 20]. Only 18% ‘ 2% of the control group had a =50% reduction in average pain at the same assessment point.

A pulse generator sends a low-threshold electric current through an extension wire to an electrode placed in the epidural space. Generated non-nociceptive signals (A’ fibers) mask the travel of nociceptive signals (Ad and C-fibers) to the brain, thus causing pain relief. It binds to presynaptic cholinergic nerve terminals and decreases the release of acetylcholine, causing neuromuscular block [55]. A randomized controlled trial reflects significant relief in neuropathic pain with subcutaneous injections [55].

A detailed discussion on the pathophysiology of neuropathic pain is out of the scope of this article; however, this is described elsewhere in the literature [8,16,27]. A minimally invasive procedure using traditional Chinese therapy based on real experiences has proven beneficial and cost-effective in managing diabetic peripheral neuropathy, back pain, and shoulder pain [96, 97]. This involves the stimulation of specific points on the body, most often by inserting thin needles through the skin, promoting the body’s natural self-healing process. Acupuncture was found to be an effective treatment option for diabetic and human immunodeficiency virus-related peripheral neuropathy, especially in Bell’s palsy and carpal tunnel syndrome [98’100]. Battlefield acupuncture (BFA) is an emerging method of easing neuropathic pain, purported to influence central nervous system pain processing through the release of ‘-endorphins and its effect on a somatotopic organization of the body represented in the auricle. In summary, clinical trial evidence for the efficacy of nonpharmacological therapies in DPN remains rudimentary.

In most cases, neuropathic pain has been understood as a combination of positive and negative symptoms. A single symptom cannot predict neuropathic pain, but certain symptoms, along with bedside findings and pain descriptors, elevate the probability of identifying a neuropathic pain-like state. Due to peripheral sensitization, lowest price there is an increased reactivity of C-fibers to the stimuli, which causes the release of glutamate that acts on the N-methyl-D-aspartate (NMDA) receptors, showing central sensitization. At the same time, there is an increase in the release of substance P, which also facilitates central sensitization.