Electrical skin measurements at acupuncture points (acupoints) have been utilized as a diagnostic and therapeutic aid for more than 50 years. Although acupoints are described as having distinct electrical properties, such as high conductance and low impedance, the underlying mechanisms are currently unknown. The present study investigated in a rat model of hypertension whether the high conductance at acupoints is a result of the release of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) during neurogenic inflammation in the referred pain area. When plasma extravasation from neurogenic inflammation was examined by exploring the leakage of intravenously injected Evans blue dye (EBD) to the skin, extravasated EBD was found most frequently in acupoints on the wrist. The increased conductance and temperature at these acupoints occurred during the development of hypertension. The increase in conductance and plasma extravasation at acupoints in hypertensive rats was ablated by cutting median and ulnar nerves, blocking small diameter afferent fibers with resiniferatoxin (RTX) injection into median and ulnar nerves, or antagonizing SP or CGRP receptors in acupoints. In turn, intradermal injection of SP or CGRP resulted in increased conductance and plasma extravasation in naïve rats. Elevated levels of SP and CGRP were found in the acupoints of hypertensive rats. These findings suggest that the high conductance at acupoints is due to vascular leakage following local release of SP and CGRP during neurogenic inflammation.

Acupuncture has been used to treat a variety of diseases and symptoms for more than 2,500 years. While a number of studies have shown that nerves are responsible for initiating the effects of acupuncture, several lines of study have emphasized the role of connective tissue in the initiation of acupuncture signals. To determine whether nerves or connective tissue mediate the action of acupuncture, we constructed a robotic acupuncture needle twister that mimicked the twisting of the needle by an acupuncturist, and we examined the role of nerves and connective tissues in the generation of acupuncture effects in rat cocaine-induced locomotion, stress-induced hypertension, and mustard oil-induced visceral pain models. Robotic or manual twisting of acupuncture needles effectively suppressed cocaine-induced hyperactivity, elevated systemic blood pressure or mustard oil-induced visceral pain in rats. These acupuncture effects were completely abolished by injecting bupivacaine, a local anesthetic, into acupoints. However, disruption of connective tissue by injecting type I collagenase into acupoints did not affect these acupuncture effects. Our findings suggest that nerve tissue, but not connective tissue, is responsible for generating the effects of acupuncture.

Adolescent cocaine exposure (ACE) increases risk of developing psychiatric problems such as anxiety, which may drive relapse in later life, however, its underlying molecular mechanism remains poorly understood.