Central δ‐opioid receptor interactions and the inhibition of reflex urinary bladder contractions in the rat

Dray, A.; Nunan, Linda M.; Wire, William S.

doi:10.1111/j.1476-5381.1985.tb10569.x

Cited by 43 publications

(24 citation statements)

References 43 publications

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“…However, the reduction of ICI was significantly smaller in vHPPE-injected rats compared with vHGinjected rats, indicating that vHPPE-mediated hPPE gene transfer has inhibitory effects on bladder overactivity induced by nociceptive stimuli without affecting normal micturition. As opioid receptors in the CNS including the spinal cord are known to be involved in the inhibitory control of the micturition reflex (Hisamitsu and de Groat, 1984;Dray et al, 1985), we examined if the antinociceptive effects of vHPPEmediated hPPE gene transfer is centrally mediated using Nal-H, which passes through the BBB, and Nal-M, which does not pass through the BBB. We found that Nal-H, but not Nal-M, antagonized the inhibitory effect of hPPE gene transfer on RTx-induced bladder overactivity (Fig.…”

Section: Figmentioning

confidence: 99%

Effects of Herpes Simplex Virus Vector–Mediated Enkephalin Gene Therapy on Bladder Overactivity and Nociception

et al. 2013

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We previously reported the effects of herpes simplex virus (HSV) vector-mediated enkephalin on bladder overactivity and pain. In this study, we evaluated the effects of vHPPE (E1G6-ENK), a newly engineered replication-deficient HSV vector encoding human preproenkephalin (hPPE). vHPPE or control vector was injected into the bladder wall of female rats 2 weeks prior to the following studies. A reverse-transcription PCR study showed high hPPE transgene levels in L6 dorsal root ganglia innervating the bladder in the vHPPE group. The number of freezing behaviors, which is a nociceptive reaction associated with bladder pain, was also significantly lower in the vHPPE group compared with the control group. The number of L6 spinal cord c-fospositive cells and the urinary interleukin (IL)-1b and IL-6 levels after resiniferatoxin (RTx) administration into the bladder of the vHPPE group were significantly lower compared with those of the control vector-injected group. In continuous cystometry, the vHPPE group showed a smaller reduction in intercontraction interval after RTx administration into the bladder. This antinociceptive effect was antagonized by naloxone hydrochloride. Thus, the HSV vector vHPPE encoding hPPE demonstrated physiological improvement in visceral pain induced by bladder irritation. Gene therapy may represent a potentially useful treatment modality for bladder hypersensitive disorders such as bladder pain syndrome/interstitial cystitis.

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Section: Figmentioning

confidence: 99%

Effects of Herpes Simplex Virus Vector–Mediated Enkephalin Gene Therapy on Bladder Overactivity and Nociception

et al. 2013

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“…and it has been clarified that its main sites of action are the supraspinal and spinal micturi tion centers and that the opioid receptors involved are of the mu and delta subtypes (2)(3)(4)(5)(6)(7)(8)(9)(10). In the brainstem reticular formation of the mid brain, pons and medullaoblongata, detrusor motor centers are located; and in the sacral parasympathetic nucleus of segments S2 to S4, parasympathetic preganglionic cell bodies innervating the bladder and internal sphincter are found (14).…”

Section: Discussionmentioning

confidence: 99%

“…However, most of the experiments used to study the effects of morphine on urinary bladder contraction have been performed in urethra-cannulated rats, so that it was not possible to observe micturition and retention of urine (2)(3)(4)(5)(6)(7)(8)(9)(10). Recently, we (11-13) de veloped a method for recording the bladder contraction accompanying micturition in an esthetized rats, and using this method, we investigated the effects of various drugs.…”

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A Study of Morphine-Induced Urinary Retention in Anesthetized Rats Capable of Micturition

Kontani

Kawabata

1988

Japanese Journal of Pharmacology

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Abstract-The nature of morphine-induced urinary retention was studied in anes thetized rats in which the bladder contraction accompanying micturition could be observed.Morphine (0.1 mg/kg, i.v.) prolonged the micturition interval and increased the level of micturition threshold.Morphine (1 mg/kg, i.v.) completely inhibited bladder contraction and bladder pressure was elevated until solution leaked from the penis, but the bladder pressure after inhibition by morphine (1 and 5 mg/kg, i.v.) did not significantly rise over the peak pressure level during micturi tion before injection of morphine.The inhibitory effect of morphine (1 and 5 mg/ kg, i.v.) was reversed by naloxone (0.1 mg/kg, i.v.). Morphine (5 mg/kg, 1-v.) did not increase the pressure induced by infusion of solution from near the bladder neck to the urethra.After intracerebroventricular (i.c.v.) and intrathecal (i.t.) adminis tration of morphine (1 iig), the micturition interval was prolonged and the level of micturition threshold was increased. Morphine (5 ttg, i.c.v and i.t.) inhibited bladder contraction and naloxone (5 ,ug, i.c.v. and Lt.) reversed the inhibitory effect of morphine injected by the same administration route.From these results, urinary retention induced by systematically injected morphine was considered to result from inhibition of bladder function mediated via opioid receptors of the micturition centers in the supraspinal and spinal regions.

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“…In the rat, distinct it and 6, but not K, receptors are known to be involved in central opioid modulation of bladder motility, both at supraspinal (Dray & Metsch, 1984a,b;Dray et al, 1985;Dray & Nunan, 1987;Sheldon et al, 1987) and spinal (Dray & Metsch, 1984c,d;Dray et al, 1985;Dray & Nunan, 1987;Sheldon et al, 1988) sites. However, Sheldon et al (1987; demonstrated in the rat that the identical inhibitory effects of several ni-receptor agonists on bladder motility could be antagonized differently.…”

Section: Discussionmentioning

confidence: 99%

“…This is due to complex effects on central and may be also peripheral neurogenic mechanisms controlling the micturition reflex (Dray & Metsch, 1984a,b,c,d;Hisamitsu & de Groat, 1984;Dray et al, 1985;Dray & Nunan, 1987;Sheldon et al, 1987;Berggren et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Effects of morphine metabolites on micturition in normal, unanaesthetized rats

Igawa

Westerling

Mattiasson

et al. 1993

British J Pharmacology

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1 By means of continuous cystometry in normal, unanaesthetized rats, the effects on micturition of intrathecally (i.t.) administered morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), the two main metabolites of morphine, were studied and compared with those of i.t. morphine.2 Both M6G (0.01, 0.1, and 0.5 lg) and M3G (5 pg) were found to have significant effects on micturition. Like morphine (0.1, 0.5, and 10pg), M6G was able to inhibit the micturition reflex, and produce urinary retention and dribbling incontinence in a dose-dependent manner. The potency of M6G for inhibiting micturition was approximately 10 times higher than that of morphine, and the duration of its effect was longer. All effects of M6G could be reversed by naloxone.3 M3G (5 jig) facilitated the micturition reflex, resulting in decreases in bladder capacity and micturition volume, and an increase in spontaneous contractile activity. Pretreatment with naloxone (10 fig), which by itself had no effect on micturition, enhanced the facilitatory effects of M3G. In addition, M3G tended to counteract the inhibitory effects of both morphine and M6G on micturition. M3G (5 jg) also produced an excitatory behavioural syndrome. 4 It is concluded that in rats, i.t. M3G has excitatory effects on micturition and behaviour, probably not mediated via opioid receptors. I.t M6G has a potent inhibitory effect on micturition mediated by stimulation of opioid receptors. It may have effects on somatosensory afferent input in lower doses than those required for effects on micturition.

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Central δ‐opioid receptor interactions and the inhibition of reflex urinary bladder contractions in the rat

Cited by 43 publications

References 43 publications

Effects of Herpes Simplex Virus Vector–Mediated Enkephalin Gene Therapy on Bladder Overactivity and Nociception

Effects of Herpes Simplex Virus Vector–Mediated Enkephalin Gene Therapy on Bladder Overactivity and Nociception

A Study of Morphine-Induced Urinary Retention in Anesthetized Rats Capable of Micturition

Effects of morphine metabolites on micturition in normal, unanaesthetized rats

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