Effects of a Mixture of Peptidase Inhibitors (Amastatin, Captopril and Phosphoramidon) on Met-Enkephalin-, β-Endorphin-, Dynorphin-(l-13)- and Electroacupuncture-Induced Antinociception in Rats

Abstract

ABSTRACT-The effects of a mixture of three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon, on methionine-enkephalin (Met-enk)-, j3-endorphin (p-end)-, dynorphin-(1 13) (Dyn) and electroacupuncture (EA)-induced antinociception were compared in rats. EA was performed by passing electric pulses (3 Hz, 0.1-msec duration, for 45 min) through acupuncture needles inserted into the Hoku point. The antinociceptive effect was estimated by the hind paw pressure test. The antinociceptive effects of Met-enk and p-end injected i.c.v. or Lt. and of Dyn injected i.t. were clearly potentiated by the PIs pretreated by the same administration routes as used for the injection of opioid peptides. The antinocicep tive effects of Met-enk, n-end and Dyn injected i.c.v. were also potentiated significantly by i.t.-PIs. PIs in jected into the periaqueductal gray (PAG) potentiated EA antinociception. However, the EA effect was not affected by i.t.-PIs and was rather attenuated by i.c.v.-PIs. These results suggest that: i) Met-enk hydro lyzing enzymes are involved in the degradation of not only Met-enk but also p-end and Dyn in the rat central nervous system; ii) Met-enk and n-end act on both supraspinal and spinal sites, while Dyn acts only on the spinal site; iii) EA antinociception is mediated by supraspinal Met-enk and/or n-end; and iv) an anti-opiate peptide system may be activated by EA stimulation, being susceptible to Met-enk hydrolyzing enzymes.

Opioidergic orofacial antinociception induced by electroacupuncture at acupoint St36

“…Earlier studies demonstrated that stimulation of acupoint LI4 induced analgesia in humans (20,21,(30)(31)(32), and antinociception in animals (33,34). However, the current results showed no similar orofacial effect of acupoint LI4 in these animals.…”

Analgesic Mechanism of Electroacupuncture in an Arthritic Pain Model of Rats: A Neurotransmitter Study

“…The analgesic effect of EA is largely decreased by blocking the opioid receptors in periaqueductal grey (PAG) matter with naloxone or antibodies against µ- or δ-receptors 11. The microinjection of the mixed peptidase inhibitors of amastatin, captopril and phosphoramidon into the PAG prevents hydrolysis of an enzyme-induced degradation of endogenous opioid peptides, potentiating the effects of acupuncture analgesia 13. In the current study, EA induced analgesic effect was also blocked by naloxone.…”

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

“…Thus, intrathecal Leu-enkephalin failed to produce analgesia in the tail-flick test, even at high doses (100 nmol), but it produced analgesia at low very doses (0.3 nmol) when it was co-injected with peptidase inhibitors (Chen et al, 2007). Another study (Kishioka et al, 1994) found that peptidase inhibitors substantially increased the analgesia produced by Metenkephalin, dynorphin or electroacupuncture. The high susceptibility of enkephalins (Guyon et al, 1979;Hiranuma et al, 1998b) and dynorphins (Hiranuma et al, 1998a;Numata et al, 1988) to peptidase degradation is well-known, and prompted the development of peptidase inhibitors as analgesics (Noble et al, 1992a;Noble et al, 1992b;Noble et al, 1997).…”