Effects and mechanisms of acupuncture analgesia mediated by afferent nerves in acupoint microenvironments

Chronic pain is one of the most prevalent medical conditions worldwide and affects millions of people, significantly limiting their quality of life. Although effective pharmacological treatments exist, such as nonsteroidal anti-inflammatory drugs and opioids, they frequently cause serious side effects, including dependence, gastrointestinal problems, and overdose risk. In this context, acupuncture has been consolidated as a promising therapeutic alternative, offering pain relief without the risks associated with conventional medications. The World Health Organization has expanded the list of diseases that acupuncture can treat to 91 conditions, including multiple types of pain.

The analgesic effect of acupuncture has been extensively documented in randomized clinical trials for various conditions, ranging from cancer pain to rheumatoid arthritis and migraine.

This study aimed to analyze the patterns and mechanisms of acupuncture-induced analgesia, with specific focus on the role of afferent nerve fibers present in the acupoint microenvironment. The researchers conducted a systematic narrative review, using the PubMed and Web of Science databases to identify studies published between 2003 and 2023. The search included terms related to acupuncture, nerve fibers, and pain, initially yielding 715 articles. After careful selection following rigorous inclusion and exclusion criteria, 91 basic studies that specifically investigated acupuncture's effects on afferent fibers and analgesia were analyzed.

The methodology included detailed analysis of studies that employed different acupuncture modalities, including manual acupuncture, electroacupuncture, and transcutaneous electrical acupoint stimulation, across various experimental pain models.

The results revealed a complex mechanism by which acupuncture produces analgesia through activation of different types of afferent nerve fibers. The study identified that acupuncture points have a high density of primary afferent nerve fibers, including medium-diameter myelinated A fibers and unmyelinated C fibers. The research demonstrated that when acupuncture is applied at the muscle layer, analgesic effects can be induced by stimulation at the threshold intensity of A fibers. However, when applied to the cutaneous layer, analgesic effects can only be produced by stimulation at the threshold intensity of C fibers.

This finding suggests that the depth and location of stimulation are crucial factors for treatment efficacy. Electroacupuncture was shown to mainly activate A fibers, whereas manual acupuncture activates both A and C fibers, explaining the different sensations and clinical efficacies observed.

The central mechanisms of analgesia revealed that acupuncture fundamentally modifies how the nervous system processes pain signals. At the spinal cord level, acupuncture activates neurons through depolarization of afferent fibers, modulating the "pain gate" as described in the gate control theory. This theory explains that A fibers, when activated, can "close the gate" and inhibit the transmission of painful signals by C fibers. In addition, acupuncture has been shown to inhibit long-term potentiation in the spinal dorsal horn and reduce the activity of wide dynamic range neurons, which are crucial in pain information transmission.

In higher nervous centers, acupuncture inhibits neuronal activation in brain regions related to pain, creating a systemic analgesic effect that extends beyond the application site.

For patients and healthcare providers, these findings have significant clinical implications that may optimize the therapeutic use of acupuncture. The research provides evidence-based guidance for the appropriate selection of acupuncture techniques. For example, for superficial skin pain, higher stimulation intensities that activate C fibers may be required, while for deeper muscular pain, lower intensities that activate A fibers may be sufficient. The study also reveals that segmental specificity exists between pain areas and acupuncture points, where points located in the same nerve segment as the lesion require lower stimulation intensity to produce effective analgesia.

For providers, this means that treatment can be personalized based on the anatomy and specific location of the patient's pain, potentially improving therapeutic outcomes and reducing the treatment time required.

Despite the promising findings, the study has some important limitations that must be considered. The research was predominantly based on studies using animal models, and the translation of these mechanisms to humans may not be direct due to physiological and anatomical differences between species. Additionally, most of the analyzed studies focused on specific models of acute or inflammatory pain, which may not adequately represent the complex chronic pain conditions encountered in clinical practice. The study also acknowledges that gaps remain in understanding how different types of acupuncture points can activate specific subtypes of afferent nerve fibers.

The authors suggest that future research should explore advanced technologies such as single-cell RNA sequencing to better analyze primary sensory neuron subtypes and their receptor mechanisms in the dorsal root ganglion. This research establishes a solid scientific foundation for the use of acupuncture in pain management, providing valuable insights into how to optimize treatment protocols and develop more precise clinical guidelines for different painful conditions.