The "brain-gut" mechanism of postherpetic neuralgia: a mini-review

Abstract

Postherpetic neuralgia (PHN), a representative type of neuropathic pain, has attracted much research on its diagnosis and therapy at the molecular level. Interestingly, this study based on the brain-gut axis provided a novel point of view to interpret the mechanism of PHN. Past neuroanatomical and neuroimaging studies of pain suggest that the prefrontal cortex, anterior cingulate cortex, amygdala, and other regions of the brain may play crucial roles in the descending inhibition of PHN. Dominant bacterial species in patients with PHN, such as Lactobacillus, generate short-chain fatty acids, including butyrate. Evidence indicates that disturbance of some metabolites (such as butyrate) is closely related to the development of hyperalgesia. In addition, tryptophan and 5-HT in the intestinal tract act as neurotransmitters that regulate the descending transmission of neuropathic pain signals. Concurrently, the enteric nervous system establishes close connections with the central nervous system through the vagus nerve and other pathways. This review aims to investigate and elucidate the molecular mechanisms associated with PHN, focusing on the interplay among PHN, the gut microbiota, and relevant metabolites while scrutinizing its pathogenesis.

Keywords: bacteria; brain-gut axis; enteric nervous system; mechanism; microbiota; postherpetic neuralgia.

Figure 1

Complex connections between the brain and intestine in PHN patients. Varicella zoster virus (VZV) invades and damages peripheral nerves, ascending to the brain through the spinal cord. Central sensitization in the brain contributes to PHN becoming a refractory condition. This process is accompanied by changes in gut microbiota colonization, which involves mechanisms for responding to pain. Specific bacteria in the gut produce short-chain fatty acids (SCFAs), which regulate the level of neuroinflammation by modulating T-cell subsets, thereby adjusting pain sensitivity. The enteric nervous system (ENS) receives neurotransmitters such as 5-HT, which transmit nociceptive signals to the central nervous system via the vagus and splanchnic nerves. The gut metabolite kynurenine enters the central nervous system via the circulation and acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, exerting analgesic effects.