Excitatory amino acid receptor antagonists and electroacupuncture synergetically inhibit carrageenan-induced behavioral hyperalgesia and spinal fos expression in rats

Abstract

The interaction between electroacupuncture and an N-methyl-D-aspartic acid (NMDA) receptor antagonist, (DL-2-amino-5-phosphonopentanoic acid; AP5), or an (+/-)-alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainite (AMPA/KA) receptor antagonist, (6,7-dinitroquinoxaline-2,3 (1H,4H); DNQX) administered intrathecally on carrageenan-induced thermal hyperalgesia and spinal c-Fos expression was investigated. The latency of paw withdrawal (PWL) from a thermal stimulus was used as a measure of hyperalgesia in awake rats. Intrathecal (i.t.) injection of 1 and 10 nmol AP5, but not DNQX, markedly increased the PWL of the carrageenan-injected paw. At a dose of 100 nmol, either AP5 or DNQX significantly increased the PWL of carrageenan-injected paw, with AP5 being more potent. The PWLs of the non-injected and normal saline (NS)-injected paws were not detectably affected by the administration of NMDA or AMPA/KA receptor antagonists at the doses tested. Unilateral electroacupuncture stimulation of the 'Zu-San-Li' (St 36) and 'Kun-Lun' (UB 60) acupuncture points (60 and 2 Hz alternately, 1-2-3 mA) contralateral to the carrageenan-injected paw significantly elevated the PWLs of carrageenan- and NS-injected paws. Although neither i.t. injection of 0.1 nmol AP5 nor 1 nmol DNQX alone had an effect on the PWL of the carrageenan- and NS-injected paws, both significantly potentiated electroacupuncture-induced analgesia in carrageenan-injected rats, especially 0.1 nmol AP5. Fos expression evoked by intraplantar (i.pl.) injection of carrageenan was examined in the spinal cord with immunohistochemical methods. Three hours after i.pl. injection of carrageenan, the number of Fos-like immunoreactive (Fos-LI) neurons was significantly increased in all the layers of the ipsilateral spinal cord at L(4-5), with the highest density in laminae I-II and V-VI. Intrathecally pre-administered AP5 (10 nmol) or DNQX (100 nmol) significantly reduced the total number of carrageenan-induced Fos-LI neurons. The reduction was most apparent in laminae I-II and IV-V. Similarly, following bilateral electroacupuncture stimulation of the 'Zu-San-Li' and 'Kun-Lun' acupuncture points, the numbers of carrageenan-induced Fos-LI neurons in laminae I-II and V-VI were also markedly reduced. When a combination of electroacupuncture with 10 nmol AP5 or 100 nmol DNQX was used, the level of Fos expression in the spinal cord induced by carrageenan was significantly lower than electroacupuncture or i.t. injection of AP5 or DNQX alone. These results demonstrate that electroacupuncture and NMDA or AMPA/KA receptor antagonists have a synergetic anti-nociceptive action against inflammatory pain. Furthermore, this study supports the idea that both NMDA and AMPA/KA receptors are involved in spinal nociceptive transmission in carrageenan-inflamed rats, with the former more preferentially mediating transmission of nociceptive information from cutaneous tissue.

Is functional state of spinal microglia involved in the anti-allodynic and anti-hyperalgesic effects of electroacupuncture in rat model of monoarthritis?

“…Acupoint Stimulator (LH-202H, Huawei Co., Ltd., Beijing, China). The electroacupuncture parameters were set as follows: square wave current output (pulse width: 0.2 ms); intensities ranging from 1-2-3 mA (each intensity for 10 min, totaling 30 min); at a 100 Hz and 2 Hz alternating frequencies (automatically shifting between 100 Hz and 2 Hz stimulation for three seconds each) (Zhang et al, 2002). Sham EA control animals received needle insertion into GB30 and GB34 similar to EA treatment, but without electrical stimulation.…”

Electroacupuncture suppresses hyperalgesia and spinal Fos expression by activating the descending inhibitory system

“…Recent chronic pain acupuncture/ electroacupuncture (EA) studies, including our own (Lao et al, 2004), have shown that EA produces anti-hyperalgesia in ankle sprain and inflammatory pain animal models (Koo et al, 2002;Zhang et al, 2002). Although our study *Corresponding author: Dr. Rui-Xin Zhang, Center for Integrative Medicine, University of Maryland, School of Medicine, HSF-2, Room S209, 20 Penn Street, Baltimore, MD 21201, Telephone: 410-706-1582, Fax: 410-706-1583, E-mail:Rzhan001@umaryland.edu.…”

Effect of acupuncture on TNF-alpha, IL-<FONT FACE=Symbol>1b</FONT> and IL-10 concentrations in the peritoneal exudates of carrageenan-induced peritonitis in rats

“…Acupuncture treatment reduces both the number of inflammatory cells and volume of exudate in several inflammatory models, such as carrageenan injection in the air pouch of rats, turpentine in rabbit ears, carrageenan-induced paw oedema, carrageenaninduced pleurisy, Freund's adjuvant-induced rheumatoid arthritis, sepsis and chemical peritonitis in rats (SIN et al, 1983;SIN, GWEE & LOH, 1984;SIN, 1986;KENDALL, 1989;QINGLAN, 1991;CECCHERELLI et al, 1999;KWON, et al, 2001;KWON, et al, 2002;ZHANG et al, 2002;SCOGNAMILLO-SZABÓ et al, 2004;SCOGNAMILLO-SZABÓ et al, 2004). Supporting these data, clinical trials confirm the efficacy of acupuncture treatment on allergic rhinitis, pruritic dermatosis, bronchial asthma, eczema, rheumatoid arthritis and other disorders (TOWNSEND et al, 1999;TUMACHI, 1999;CASIMIRO et al, 2002;PETTI et al, 2002;STEURER-STEYA;RUSSIB & STEURERC, 2002;BIELORY & HEIMALL, 2003;MADSEN et al, 2003;MCCARNEY et al, 2004).…”