Efficacy of a Combination of N-Palmitoylethanolamide, Beta-Caryophyllene, Carnosic Acid, and Myrrh Extract on Chronic Neuropathic Pain: A Preclinical Study

Abstract

Neuropathic pain (NP) is a common public health problem that poses a major challenge to basic scientists and health-care providers. NP is a complex problem with an unclear etiology and an often-inadequate response to current medications. Despite the high number of drugs available, their limited pharmacological efficacy and side effects hamper their chronic use. Thus, the search for novel treatments is a priority. In addition to pharmaceuticals, natural extracts and food supplements are often used to help treating patients with NP. One such supplement is Noxiall ® , a commercially available combination of N-Palmitoylethanolamide (PEA), beta-caryophyllene; carnosic acid and myrrh. Here, we compare the efficacy of Noxiall ® to that of the medications gabapentin and pregabalin in the NP model of chronic constriction injury (CCI) using sciatic nerve ligation in mouse. Following CCI, mice developed a significant increase in mechanical allodynia and thermal hyperalgesia. Results showed that administration of either Noxiall ® , pregabalin, or gabapentin significantly attenuated mechanical allodynia. The magnitude of the Noxiall ® effect was comparable to that of gabapentin or pregabalin. In addition, co-administration of non-effective doses of pregabalin and Noxiall ® resulted in a significant decrease in NP, suggesting an additive efficacy. Noxiall ® was efficacious also in reducing CCI-induced thermal hyperalgesia. These findings support the rationale of using natural remedies in conjunction with classical pharmacological agents to treat chronic NP.

Salix tetrasperma Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway

“…Gabapentinoids like pregabalin and gabapentin represent a first-line treatment in chronic neuropathic pain and represent one of the most widely used drugs to control this condition. However, patients usually used higher doses for pain control which resulted in wide range of adverse effects [24].…”

Carnosic acid improves porcine early embryonic development by inhibiting the accumulation of reactive oxygen species

“…CA is widely used as a food preservative and protective agent, and it is used in the nutritional healthcare and cosmetic industries due to its fragrance and antibacterial activity. In addition, studies have shown that CA can reduce lipid oxidation, and exhibits great potential for the protection of nerves and the treatment of obesity-related diseases [ 17 , 18 , 19 ]. However, its effects on mammalian reproductive processes, especially in female ovarian development and early embryonic development, are still unclear.…”

Influence of methadone on the anticonvulsant efficacy of valproate sodium gabapentin against maximal electroshock seizure in mice by regulation of brain MDA TNF-α

“…However, valproate exerts its effects by increasing the concentrations of GABA via inhibiting its metabolism and increasing its synthesis ( 75 ). Therefore, there is still a significant and positive association between an increase in the oxidative stress markers and a decrease in the antioxidant levels with the number of seizures in valproate monotherapy ( 65 ).…”