Analgesic Effects Elicited by Neuroactive Mediators Injected into the ST 36 Acupuncture Point on Inflammatory and Neuropathic Pain in Mice.

The present study evaluates whether the injection of serotonin, acetylcholine, glutamate, bradykinin, histamine, or substance P (SP) into the Zusanli (Stomach 36, ST 36) acupoint can also produce the acupuncture-induced antinociceptive effect on inflammatory or neuropathic pain. In this in vivo experimental study, a total of 450 male Swiss mice were used. Mice were injected with saline or complete Freund's adjuvant (CFA) or subjected to sham or chronic constriction injury (CCI) surgery. After the establishment of the inflammatory (4 hours) or the neuropathic pain (3 days), the animals (n = 6) received manual acupuncture, sham acupuncture, or injection of saline, serotonin, acetylcholine, glutamate, bradykinin, histamine, or SP into the ST 36 and were evaluated for up to 24 hours. Mechanical threshold was evaluated, and the L4-L6 dorsal root ganglion was used for analysis of the transient receptor potential vanilloid type 1 overexpression. The mice from both the CFA and CCI models treated with manual acupuncture had significant increases in the thresholds for more than 24 hours. Sham acupuncture stimulation did not change the thresholds. In the mice injected with each of the mediators, the thresholds were significantly increased for all times in both the CFA and CCI models. Transient receptor potential vanilloid type 1 overexpression in CFA and CCI mice was reduced at all times by injection of serotonin, acetylcholine, or SP but not by injection of glutamate, histamine, or bradykinin. Our data suggest that the neuroactive mediators released by acupuncture-induced tissue injury may contribute to acupuncture-induced analgesia.

Antinociceptive effects of low-level laser therapy at 3 and 8 j/cm2 in a rat model of postoperative pain: possible role of endogenous Opioids.

Low-level laser therapy (LLLT) is the direct application of light to stimulate cell responses (photobiomodulation) to promote tissue healing, reduce inflammation, and induce analgesia; the molecular basis for these effects of LLLT remains unclear. The objective of this study was to evaluate the analgesic effect of LLLT in the rat plantar incision model of postoperative pain as well as to investigate some of the possible mechanisms involved in this effect. Wistar rats were submitted to plantar incision and treated with LLLT (830 nm, continuous-mode, 30 mW/cm2 , 1-12 J/cm2 ). Postoperative thermal and mechanical hypersensitivity were monitored for 24 hours post-incision. In addition, the animals were pretreated with saline, naloxone (a nonselective opioid receptor antagonist; 20 µg/5 µl) or methysergide (5-HT2C , 5-HT2A , 5-HT7 , 5-HT5a , 5-HT6, and 5-HT1F receptors antagonist; 30 µg/5 µl). Moreover, 24 hours after incision and treatment, the TNF-α and IL-1ß levels in serum were evaluated. Our results demonstrate, for the first time, that LLLT at 3 or 8 J/cm2 , but not at 1-2, 4-7, or 9-12 J/cm2 , induced an analgesic effect on postoperative pain. Naloxone, but not methysergide, blocked the LLLT-induced anti-nociceptive effect. Additionally, IL-1-ß and TNF-α production significantly decreased after LLLT at 3 or 8 J/cm2 . Our results suggest that LLLT at 3 or 8 J/cm2 primarily modulates the endogenous opioids system and is not directly mediated by serotonergic receptors. Reduction of IL-1ß and TNF-α may play a role in the antinociceptive action of LLLT. Lasers Surg. Med. 49:844-851, 2017. © 2017 Wiley Periodicals, Inc.

Analgesia induced by 2- or 100-Hz electroacupuncture in the rat tail-flick test depends on the anterior pretectal nucleus.

AIMS: The anterior pretectal nucleus (APtN) and electroacupuncture (EA) activate descending mechanisms to modulate nociceptive inputs in the spinal dorsal horn. This study examines qualitatively whether mechanisms in the APtN participate in the EA-induced analgesia in rats. MAIN METHODS: The tail-flick test was utilized to examine the changes produced by non-selective antagonists of serotonergic (methysergide, 37 pg), muscarinic (atropine, 10 ng) and opioid (naloxone, 10 ng) receptors; selective antagonists against µ (CTOP, 6.4 µg), δ (ICI174,864, 6.9 µg) or κ (nor-BNI, 7.3 µg); 5HT1 (methiothepin, 0.47 µg), 5HT2 (ketanserin, 5.4 µg), or 5HT3 (MDL 72222, 15.7 µg); and GABAA (bicuculline, 150 ng) receptors injected into the dorsal (d) or ventral (v) APtN on the antinociception induced by a 20-min EA applied at 2- or 100-Hz frequency to the Zusanli and Sanyinjiao acupoints. KEY FINDINGS: The 2-Hz EA-induced analgesia was blocked by naloxone, CTOP or atropine, was less intense after bicuculline, was shorter after methysergide or methiothepin in dAPtN, and was less intense after methysergide, methiothepin and bicuculline in vAPtN. The 100-Hz EA-induced analgesia was less intense after methysergide, methiothepin and CTOP in vAPtN, and remained unchanged after injection of the antagonists into the dAPtN. SIGNIFICANCE: The 2-Hz EA-induced analgesia utilizes cholinergic muscarinic, µ-opioid, GABAA and 5-HT1 mechanisms in the dAPtN and µ-opioid and 5-HT1 mechanisms in the vAPtN, while 100-Hz EA-induced analgesia utilizes µ-opioid and 5-HT1 mechanisms in the vAPtN but does not utilize them in the dAPtN.