Nociceptin (1-7)

Objective:To study the expression of nociceptin in adenomyosis tissue and understand its relationship with the severity of dysmenorrhea.Methods:The myometrial specimens were collected from 55 patients undergoing hysterectomy at our hospital during December 2007 and June 2008. Their mean age was 41 - 52 years old. There were 34 adenomyosis patients in case group and 21 other patients in control group. Immunohistochemical staining was employed to detect nociceptin in eutopic endometrium and ectopic endometrial tissues in case group and normal endometrium and myometrial tissues in control group.Results:The expression of nociceptin was significantly higher in the eutopic endometrial tissue (7.1 ± 1.7) of case group than those in endometrial (2.7 ± 2.0) and myometrial tissues of control group (P < 0.05); The expression of nociceptin was higher in the eutopic endometrial tissue (7.4 ± 1.5) of dysmenorrhea group than that of non-dysmenorrhea group (5.0 ± 1.2) in case group (P < 0.05); The expression of nociceptin in eutopic endometrium and myometrium was the highest in severe dysmenorrhea group (8.4 ± 1.3). And the non-dysmenorrhea and mild dysmenorrheal groups had no significant differences [(5.0 ± 1.2) vs (6.8 ± 1.4)]. And it decreased gradually in moderate dysmenorrhea, mild dysmenorrhea and non-dysmenorrhea groups.Conclusion:A high expression of nociceptin in adenomyosis may be one of the casual factors of dysmenorrhea. The severity of dysmenorrhea is positively correlated with the expression of nociceptin in eutopic endometrial tissue in case group (r = 0.515, P = 0.034) and ectopic endometrium tissue. And the endometrial expression of nociceptin may be monitored dynamically to track the development of adenomyosis.

Nociceptin and its N-terminal fragment, nociceptin (1 7), were administered intrathecally (i.t.) into conscious mice. Nociceptin (3.0 fmol) produced a significant reduction in the nociceptive thermal threshold (hyperalgesia) measured as the tail-flick and paw-withdrawal responses. Nociceptin (1-7), injected i.t., at 150-1200 fmol had no significant effect. However, when nociceptin (1-7) (150 1200 fmol) was injected simultaneously with nociceptin (3.0 fmol), nociceptin-induced hyperalgesia was significantly reduced. Analgesia induced by a high dose (1200 pmol) of nociceptin was not antagonized by co-administration of nociceptin (1-7) (1200 fmol). These results suggest that N-terminal fragments of nociceptin formed endogenously could modulate the hyperalgesic action of nociceptin in the spinal cord.

The N-terminal substance P fragment SP(1-7) is known to modulate hyperalgesia and opioid withdrawal in animal models. This study examined the effects of intraperitoneal (i.p.) injections of SP(1-7) on chronic morphine tolerance and on the levels of dynorphin B (DYN B) and nociceptin/orphanin FQ (N/OFQ) in various brain areas of male Sprague-Dawley rats. Morphine tolerance was induced by subcutaneous injections of the opioid (10mg/kg) twice daily for 7 days. SP(1-7) injected i.p. (185 nmol/kg) 30 min prior to morphine reduced the development of morphine tolerance. Immunoreactive (ir) DYN B and N/OFQ peptide levels were measured in several areas of the central nervous system. Levels of ir DYN B in rats treated with SP(1-7) and morphine were decreased in the nucleus accumbens, substantia nigra and ventral tegmental area and increased in the frontal cortex. The ir N/OFQ levels were increased in the periaqueductal gray and decreased in the nucleus accumbens. Since the concentration profiles of the two peptides were altered by SP(1-7) in the areas that are implicated in the modulation of opioid tolerance and analgesia, it is suggested that DYN B and N/OFQ systems may be involved in the effects of SP(1-7) on opioid tolerance.