![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
NEUROPHARMACOLOGY
Department of Anesthesiology, Graduate School of Medicine, Chiba University, Chiba, Japan
Received for publication
December 30, 2005
Accepted
March 23, 2006.
 |
Abstract |
|---|
 Top Abstract Materials and MethodsResultsDiscussionReferences |
|---|
). Buprenorphine has been reported to have high affinities for µ-, 
-, and 
-opioid receptors with Ki values in the nanomolar range. (Huang et al., 2001).
Recently, buprenorphine has been reported to act as an agonist at opioid receptor like-1 (ORL1) receptors (Bloms-Funke et al., 2000). Lutfy et al. (2003) reported that the antinociceptive effect of subcutaneously administered buprenorphine was markedly enhanced in mice lacking ORL1 receptors in the tail-flick test and that systemic administration of an ORL1 receptor antagonist enhanced the analgesic effect of s.c. administered buprenorphine. Mice lacking µ-opioid receptors failed to exhibit an antinociceptive effect after s.c. administration of buprenorphine (Lutfy et al., 2003). Moreover, buprenorphine did not produce an analgesic effect in µ1-opioid receptor-deficient mice (Kamei et al., 1997). These data suggest that the antinociceptive effect of systemically administered buprenorphine is mediated by the activation of µ-opioid receptors and that the analgesic effect of systemically administered buprenorphine is suppressed by concomitant activation of ORL1 receptors. On the other hand, spinal ORL1 receptor activation has been reported to produce an analgesic effect (Yamamoto et al., 1997, 1999). µ-Opioid receptors and ORL1 receptors are widely located in the nervous system, and there are not enough data to determine which µ-opioid receptor plays an important role in producing an analgesic effect of buprenorphine and which ORL1 receptor plays an important role in suppressing an analgesic effect of buprenorphine when buprenorphine is administered systemically. Moreover, it is possible that the analgesic effect of systemically administered buprenorphine can be attributed to the activation of spinal ORL1 receptors. In the present study, we investigated the analgesic effect of intrathecal (i.t.), intracerebroventricular (i.c.v.), or i.p. administration of buprenorphine and the effect of naloxone (a µ-opioid receptor antagonist) or J113397 (an ORL1 receptor selective antagonist) on the analgesic effect of i.t., i.c.v., or i.p. administered buprenorphine in the rat formalin test.
Expression of Fos, which is the protein product of the immediate-early proto-oncogene c-fos, has been widely used to identify populations of neurons that are activated by noxious stimuli (Hunt et al., 1987) and to concomitantly examine the ability of drugs to suppress the expression of Fos-like immunoreactivity (Fos-LI) in the spinal cord in the formalin test (Hammond et al., 1998; Yamamoto et al., 2002). In the present study, we also examined the effect of i.t., i.c.v., or i.p. administration of buprenorphine on the expression of Fos-LI induced by paw formalin injection.
|
Materials and Methods |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Intrathecal Catheters and Intracerebroventricular Cannulas
Chronic i.t. catheters were inserted by passing a PE-10 catheter through an incision in the atlanto-occipital membrane to a position 8 cm caudal to the cisterna at the level of lumbar enlargement (Yaksh and Rudy, 1976). The animals were allowed to recover for 1 week before experimental use.
For i.c.v. injection, a stainless steel thin-wall injection cannula (24 gauge, 0.64 mm o.d., 15 mm long) was stereotaxically placed through a burr hole (0.5 mm caudal to the coronal suture and 1 mm lateral to the sagittal suture; 3 mm deep to the dura) into right lateral ventricle. The animals were allowed to recover for 3 days before experimental use. Rats showing neurological deficits were not studied.
Formalin Test
To carry out the formalin test, 50 µl of 5% formalin was injected s.c. into the dorsal surface of the right hindpaw with a 27-gauge needle under brief halothane anesthesia. Within 1 min after the formalin injection, spontaneous flinching of the injected paw could be observed. Flinching is readily discriminated and is characterized as a rapid and brief withdrawal or flexion of the injected paw. This pain-related behavior was quantified by counting the number of flinches for 1-min periods at 1 to 2 and at 5 to 6 min and then for 1-min periods at intervals during the period from 10 to 60 min after the injection. Two phases of spontaneous flinching behavior (an initial acute phase (phase 1, during the first 6 min after the formalin injection) and a prolonged tonic phase (phase 2, beginning 
10 min after the formalin injection) were observed. After the observation period, the animals were immediately killed with an overdose of barbiturate.
Immunohistochemistry
Under pentobarbital anesthesia, surgery proceeded with sternotomy, transcardiac aortic needle cannulation, and perfusion with 500 ml of 4% paraformaldehyde in 0.1 M phosphate buffer (pH = 7.4). Spinal cords were removed and postfixed in the same fixative solution overnight at 4°C. After storing in 0.01 M phosphate-buffered saline (PBS) containing 20% sucrose for 8 h at 4°C, the L4-L5 spinal cord was sectioned to a 40-µm thickness on a cryostat. The sections were processed for Fos immunohistochemistry by a free-floating avidin-biotin complex technique using rabbit antibody to Fos (1: 1000; Santa Cruz Biotechnology, Santa Cruz, CA) diluted with PBS containing 5% normal goat serum and 0.3% Triton X-100, for 20 h at 4°C. The sections were then incubated at room temperature for 90 min with a biotinylated goat anti-rabbit immunogloblin G (1:100; Vector Laboratories, Burlingame, CA) in PBS containing 5% normal goat serum and 0.3% Triton X-100. The sections were incubated at room temperature for 1 h in avidin-biotin complex (1:100; Vector Laboratories) and visualized with diaminobenzidine and ammonium nickel sulfate. The tissue sections were mounted onto gelatin-coated slides, air-dried, dehydrated in alcohol in a graded manner, cleared in xylene, and coverslipped.
Behavioral Analysis
Motor functions were evaluated by the performance of two specific behavioral tasks, as follows (Stevens and Yaksh, 1986).
1) The Placing/Stepping Reflex. This response was evoked by drawing the dorsum of either hindpaw over the edge of a tabletop.
2) The Righting Reflex. An animal placed horizontally with its back on the table will normally show an immediate coordinated twisting of the body around its longitudinal axis to regain its normal position on its feet.
To quantify the evaluation of motor functions, both tasks were scored on a scale of 0 to 2 in which 0 = absence of function and 2 = normal motor functions. Animals that were able to perform the motor tasks but did so more slowly than normal animals were assigned a score of 1.
Drugs
The i.t. administered drugs were delivered in a total volume of 10 µl. The i.c.v. administered drugs were delivered in a total volume of 3 µl. The i.p. administered drugs were delivered in a total volume of 1 ml. The agents used in this study were buprenorphine (Sigma Chemical, St. Louis, MO), J113397 (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one, molecular weight 436; Banyu Pharmaceutical Co., Tsukuba, Japan) (Ozaki et al., 2000) and naloxone hydrochloride (molecular weight 364; Sigma Chemical).
Experimental Protocol
Intrathecal or Intracerebroventricular Study. For the dose-response study, buprenorphine was administered i.t. or i.c.v. 10 min before the formalin injection (i.t. study: 0.1 ng, n = 5; 1 ng, n = 5; 10 ng, n = 5; i.c.v. study: 1 ng, n = 5; 10 ng, n = 5; 100 ng, n = 5). To obtain control data, vehicle (saline) was injected i.t. (n = 6) or i.c.v. (n = 5). To verify that the effect of i.t. or i.c.v. administered buprenorphine on the formalin test was produced by an interaction between buprenorphine and a spinal or a supraspinal naloxone-sensitive µ-opioid receptor or a spinal or a supraspinal J113397-sensitive ORL1 receptor, respectively, 10 µg of naloxone or 10 µg of J113397 was administered i.t. (naloxone, n = 5; J113397, n = 5) or i.c.v. (naloxone, n = 5; J113397, n = 5) 10 min before the i.t. or i.c.v. injection of buprenorphine (i.t., 10 ng; i.c.v., 100 ng). The effect of i.t. or i.c.v. administration of either 10 µg of naloxone (i.t., n = 5; i.c.v., n = 5) or 10 µg of J113397 (i.t., n = 5; i.c.v., n = 5) on the formalin test was also examined.
Intraperitoneal Study. For the dose-response study, buprenorphine was administered i.p. 10 min before the formalin injection (30 µg/kg, n = 6; 100 µg/kg, n = 5; 300 µg/kg, n = 5). To obtain control data, vehicle (saline, n = 5) was injected i.p. To verify that the effect of i.p. administered buprenorphine in the formalin test was produced by an interaction between buprenorphine and a naloxone-sensitive µ-opioid receptor, 1 mg/kg naloxone (n = 5) was administered i.p. 10 min before the i.p. injection of 300 µg/kg buprenorphine. To verify that the effect of i.p. administered buprenorphine in the formalin test was produced by an interaction between buprenorphine and a J113397-sensitive ORL1 receptor, 1 mg/kg J113397 (n = 5) was administered i.p. 10 min before the i.p. injection of 100 µg/kg buprenorphine. The effect of i.p. administration of either 1 mg/kg naloxone (n = 5) or 1 mg/kg J113397 (n = 5) on the formalin test was also examined.
To determine which naloxone-sensitive µ-opioid receptor, spinal or supraspinal, contributes to the analgesic effect of i.p. administered buprenorphine and which J113397-sensitive ORL1 receptor, spinal or supraspinal, contributes to the analgesic effect of i.p. administered buprenorphine 10 µg of naloxone or 10 µg of J113397 was administered i.t. (naloxone, n = 6; J113397, n = 5) or i.c.v. (naloxone, n = 5; J113397, n = 5) 10 min before the i.p. injection of 300 or 100 µg/kg buprenorphine. To obtain control data, vehicle (saline) was administered i.t. (n = 8), i.c.v. (n = 5), or i.p. (n = 5) 10 min before the i.p. administration of 300 or 100 µg/kg buprenorphine.
Immunohistochemical Study. Ten nanograms of buprenorphine (i.t. study, n = 6), 100 ng of buprenorphine (i.c.v. study, n = 5), or 300 µg/kg buprenorphine (i.p. study, n = 6) was administered 10 min before the formalin injection, and the expression of Fos-LI was examined 2 h after the formalin injection. For comparison, vehicle (saline) was administered i.t. (n = 5), i.c.v. (n = 5), or i.p. (n = 5).
For the quantitation of Fos-LI, five sections from the L4 and L5 segments of the spinal cord of each rat were randomly selected. The number of Fos-LI-positive neurons in the superficial laminae (laminae I and II), the nucleus proprius (laminae III and IV), and the neck of dorsal horn (lamina V) on the side of the spinal cord ipsilateral to the site of formalin injection were counted. Lamina borders were identified by use of anatomical landmarks in gray matter and standard anatomical drawings. The investigator responsible for counting the Fos-LI-positive neurons was blind to the drug treatment of each animal. The average of the number of Fos-LI-positive neurons in five slices was defined as the number of Fos-LI-positive neurons.
Statistical Analysis
Formalin Test. For the dose-response analysis, data from phase 1 (0-6 min) and phase 2 (10-60 min) observations were considered separately. In each case, the cumulative instances of formalin-evoked flinches during phase 1 and phase 2 were calculated for each rat. The percentage of vehicle control flinches during phase 1 and phase 2 was calculated in each rat, and these individual rat data were then used to construct phase 1 and phase 2 dose-response curves. To evaluate the dose dependence, one-way analysis of variance (ANOVA) was used. For multiple comparisons, Tukey's test was used. In the antagonist study, the unpaired t test (two-tailed) was used.
|
Wherever appropriate, results are expressed as means ± S.E.M. Critical values that reached a p < 0.05 level of significance were considered statistically significant.
|
Results |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Intrathecal Study. Intrathecal injection of buprenorphine decreased the sum of flinches, in both phase 1 and phase 2 flinching behavior, in a dose-dependent manner for doses between 0.1 and 10 ng (Figs. 1 and 2) (phase 1, p < 0.005; phase 2, p < 0.001, by ANOVA). Pretreatment with 10 µg of naloxone antagonized the analgesic effect of 10 ng of buprenorphine on both phase 1 and phase 2 flinching behavior (Fig. 3; Table 1) (phase 1, p < 0.01; phase 2, p < 0.01, by t test). Pretreatment with 10 µg of J113397 antagonized the analgesic effect of 10 ng of buprenorphine on the phase 1 flinching behavior but not on the phase 2 flinching behavior (Fig. 3; Table 1) (phase 1, p < 0.05; phase 2, p > 0.7, by t test). Intrathecal injection of 10 µg of naloxone or 10 µg of J113397 had no effect on the phase 1 and phase 2 flinching behavior compared with saline-treated rats (Fig. 3) (naloxone, p > 0.2; J113397, p > 0.3, by t test).
|
|
|
Intracerebroventricular Study. Intraventricular injection of buprenorphine decreased the sum of flinches in both the phase 1 and the phase 2 flinching behavior, in a dose-dependent manner at a dose between 1 and 100 ng (Figs. 1 and 2) (phase 1, p < 0.005; phase 2, p < 0.001, by ANOVA). Pretreatment with either 10 µg of naloxone or 10 µg of J113397 antagonized the analgesic effect of 100 ng of buprenorphine on both the phase 1 and the phase 2 flinching behavior (Fig. 3; Table 1) (phase 1, p < 0.01; phase 2, p < 0.01, by t test). Intracerebroventricular injection of 10 µg of naloxone or 10 µg of J113397 had no effect on the phase 1 and the phase 2 flinching behavior compared with saline-treated rats (Fig. 3) (naloxone, p > 0.1; J113397, p > 0.1, by t test).
Intraperitoneal Study. Intraperitoneal administration of buprenorphine decreased the sum of flinches in both the phase 1 and the phase 2 flinching behavior in a dose-dependent manner at a dose between 30 and 300 µg/kg (Figs. 1 and 2) (phase 1, p < 0.01; phase 2, p < 0.001, by ANOVA). Pretreatment with 1 mg/kg naloxone (i.p.) antagonized the effect of 300 µg/kg buprenorphine on the phase 1 and the phase 2 flinching behavior (Fig. 4; Table 1) (p < 0.05 by t test). Pretreatment with 1 mg/kg J113397 (i.p.) enhanced the analgesic effect of 100 µg/kg buprenorphine on the phase 2 but not on the phase 1 flinching behavior (Fig. 4; Table 1) (phase 1, p > 0.1; phase 2, p < 0.005, by t test). Intraperitoneal injection of 1 mg/kg naloxone or 1 mg/kg J113397 had no effect on the phase 1 and the phase 2 flinching behavior as compared with saline-treated rats (naloxone study, p > 0.2; J113397 study, p > 0.05 by t test (Fig. 4). Pretreatment with either 10 µg of naloxone (i.t.) or 10 µg of J113397 (i.t.) antagonized the effect of 300 µg/kg buprenorphine on the phase 1 flinching behavior but not on the phase 2 flinching behavior (Fig. 4; Table 1) (phase 1, p < 0.05; phase 2, p > 0.2, by t test).
|
Immunohistochemical Study. Either i.t. injection of 10 ng of buprenorphine or i.c.v. injection of 100 ng of buprenorphine had no effect on the number of Fos-LI-positive neurons in laminae I and II, laminae III and IV and lamina V compared with saline-treated rats (laminae I and II, p > 0.2; laminae III and IV, p > 0.1; lamina V, p > 0.1, by t test (Fig. 5). Intraperitoneal injection of 300 µg of buprenorphine decreased the number of the Fos-LI-positive neurons in laminae I and II but not in laminae III and IV, and lamina V compared with saline treated rats (laminae III and IV, p > 0.1; lamina V, p > 0.1, by t test (Fig. 5).
|
|
Discussion |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
). When the formalin test is used to elucidate drug effects, many mechanistic explanations are available. Moreover, buprenorphine has been reported to produce an analgesic effect in a dose-dependent manner in the formalin test, but in some other models, buprenorphine produced bell-shaped dose-response curves (Christoph et al., 2005). Thus, we chose the formalin test.
Intrathecal Study
Intrathecal administration of buprenorphine attenuated the flinching behavior at a dose between 0.1 and 10 ng. The lethal i.t. dose of buprenorphine is 100 ng, and we could not examine the effect of i.t. administration of this dose. Intrathecal administration of 10 µg of naloxone antagonized the analgesic effect of i.t. administration of 10 ng of buprenorphine on both phase 1 and phase 2 responses. Intrathecally administered J113397 antagonized the analgesic effect of i.t. administration of 10 ng of buprenorphine on the phase 1 response but not on the phase 2 response. These data suggest that when 10 ng of buprenorphine was administered i.t., activation of both naloxone-sensitive µ-opioid receptors and J113397-sensitive ORL1 receptors is needed to produce an analgesic effect on the phase 1 response and activation of naloxone-sensitive µ-opioid receptors is enough to produce an analgesic effect on the phase 2 response. It has been reported that i.t. administered morphine or i.t. administered nociceptin/orphanin FQ, an agonist of ORL1 receptors, decreased the number of phase 1 and phase 2 flinching behaviors in the rat formalin test (Yamamoto and Yaksh, 1992; Yamamoto et al., 1997). This finding indicates that activation of either spinal µ receptors or spinal ORL1 receptors is enough to produce an analgesic effect on the phase 1 and the phase 2 responses evoked by paw formalin injection, which suggests that i.t. administration of 10 ng of buprenorphine does not activate enough naloxone-sensitive µ receptors alone or enough J113397-sensitive ORL1 receptors alone to produce an analgesic effect on the phase 1 response. These data also indicate that naloxone-sensitive µ-opioid receptor activation alone is enough to produce an analgesic effect on the phase 2 response when buprenorphine is administered i.t., which suggests that the number of activated naloxone-sensitive µ-opioid receptors needed to produce an analgesic effect on the phase 2 response is smaller than that needed to produce an analgesic effect on the phase 1 response.
Intracerebroventricular Study
Intracerebroventricular administration of buprenorphine attenuated the flinching behavior at a dose between 1 and 100 ng. Intracerebroventricular administration of either 10 µg of naloxone or 10 µg of J113397 antagonized the analgesic effect of i.c.v. administration of 100 ng of buprenorphine on both the phase 1 and the phase 2 responses. Thus, when 100 ng of buprenorphine was administered i.c.v., activation of both µ and ORL1 receptors is needed to produce an analgesic effect and when either µ-opioid or ORL1 receptors were blocked by naloxone or J113397, the analgesic effect of i.c.v. administered buprenorphine disappeared. Wang et al. (1999) reported that i.c.v. administration of µ- and -opioid receptor agonists produced an analgesic effect on both the phase 1 and the phase 2 responses in the formalin test and that i.c.v. administration of nociceptin/orphanin FQ attenuated the brain µ- and -opioid receptor-mediated analgesia. These data strongly suggested that activation of brain ORL1 receptor suppressed brain µ-opioid receptor-mediated analgesia. We do not know the precise mechanisms that produce the analgesic effect of i.c.v. administered buprenorphine. It has been suggested that the nucleus raphe magnus of the rostral ventromedial medulla is a major site of the supraspinal nociceptin/orphanin FQ effects on pain processing. In this region both ON cells and OFF cells are located. ON cells fire immediately before a nociceptive reaction, whereas OFF cells are inhibited by the GABAergic ON cells and, therefore, are silent at the same time. Activation of OFF cells has been reported to induce spinal antinociception via descending antinociceptive tracts (Zeilhofer and Calo, 2003). Inhibition of ON cells by activation of µ-opioid receptors causes OFF cell disinhibition and results in spinal antinociception. Nociceptin/orphanin FQ inhibits both ON cells and OFF cells (Pan et al., 2000; Zeilhofer and Calo, 2003). The net effect of nociceptin/orphanin FQ on nociception at supraspinal sites depends on the activation state (resting versus sensitized) of pain controlling neuronal circuits (Zeilhofer and Calo, 2003) and the activation state of opioid receptors other than the ORL1 receptor. In the present study, i.c.v. administration of buprenorphine produced an analgesic effect by activation of both µ and ORL1 receptors.
Intraperitoneal Study
Intraperitoneal administration of buprenorphine decreased the phase 1 and the phase 2 responses at a dose between 30 and 300 µg/kg.
Effect on Phase 1 Response. Both i.t. administration of 10 µg of naloxone and i.t. administration of 10 µg of J113397 antagonized the analgesic effect of i.p. administered buprenorphine on the phase 1 response. This finding suggests that activation of both spinal naloxone-sensitive µ receptors and spinal J113397-sensitive ORL1 receptors are needed to produce an analgesic effect on the phase 1 response when buprenorphine is administered i.p.. Both i.c.v. administration of 10 µg of naloxone and i.c.v. administration of 10 µg of J113397 had no effect on the analgesic effect of i.p. administered buprenorphine on the phase 1 response, and i.p. administration of 1 mg/kg naloxone but not of 1 mg/kg J113397 antagonized the analgesic effect of i.p. administered buprenorphine on the phase 1 response. These data suggest that when buprenorphine was administered i.p., an activation of supraspinal µ and ORL1 receptors had no effect on the phase 1 response, and the analgesic effect of i.p. administered buprenorphine is mediated by the activation of both spinal µ-opioid receptors and spinal ORL1 receptors. It is not clear why i.p. administered J113397 had no effect on the analgesic effect of buprenorphine on the phase 1 response. It is possible that enough J113397 did not reach to the spinal cord to antagonize the effect of i.p. administered buprenorphine on the phase 1 response.
Effect on Phase 2 Response. Neither i.t. administration of 10 µg naloxone nor i.c.v. administration of 10 µg of naloxone had an effect on the analgesic effect of i.p. administered buprenorphine on the phase 2 response, and i.p. administration of 1 mg/kg naloxone antagonized the analgesic effect of i.p. administered buprenorphine on the phase 2 response. These data suggest that the activation of either spinal or supraspinal naloxone-sensitive µ-opioid receptors is enough to produce an analgesic effect of buprenorphine on the phase 2 response. Either i.c.v. or i.p. administration of J113397 enhanced the analgesic effect of i.p. administered buprenorphine on the phase 2 response, and i.t. administration of J113397 had no effect on the analgesic effect of i.p. administered buprenorphine on the phase 2 response. As noted above, the analgesic effect of i.c.v. administered buprenorphine on phase 1 and phase 2 responses was antagonized by i.c.v. administration of J113397. These data suggest that activation of supraspinal ORL1 receptors attenuated the spinal but not the supraspinal analgesic effect of buprenorphine on the phase 2 response. As mentioned above, the net effect of activation of ORL1 receptors on nociception at supraspinal sites strongly depends on the activation state (resting versus sensitized) of pain-controlling neuronal circuits. It has been reported that paw formalin injection induces a sensitized state during phase 2, but not during phase 1 (Yamamoto and Yaksh, 1992). In the rat formalin test, activation of supraspinal ORL1 receptors modulates the spinal analgesic effect of buprenorphine on the phase 2 but not on the phase 1 response. These data are consistent with the previous report that suppressing the ORL1 component by an antagonist increases the analgesic effect of systemically administered buprenorphine (Lutfy et al., 2003). It has been reported that systemic administration of buprenorphine produced an analgesic effect with a bell-shaped dose-response curve in the rat hot-plate test (Bryant et al., 1983) and in the rat neuropathic pain models (Christoph et al., 2005). Although Christoph et al. (2005) suggested that the shape of the dose-response curve depended on the nature of the painful stimulus, it is possible that the contribution of the ORL1 receptor component of buprenorphine produced a bell-shaped dose-response curve.
Fos Study
Intraperitoneal but not i.t. and i.c.v. administration of buprenorphine significantly decreased the expression of Fos-LI-positive neurons in laminae I and II of the L5 spinal dorsal horn. This indicated that only when buprenorphine activates both supraspinal and spinal µ-opioid receptors and supraspinal and spinal ORL1 receptors, buprenorphine suppressed the nociceptive input into the spinal dorsal horn.
In conclusion, 1) buprenorphine activates both µ receptor and ORL1 receptor, and 2) the mechanisms producing the analgesic effect of buprenorphine are very complicated and depend on the site of injection and/or on the activation state (resting versus sensitized) of pain-controlling neuronal circuits.
|
Acknowledgements |
|---|
|
Footnotes |
|---|
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
ABBREVIATIONS: ORL1, opioid receptor like-1; i.t., intrathecal(ly); i.c.v., intracerebroventricular(ly); J113397, (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one; Fos-LI, Fos-like immunoreactivity; PBS, phosphate-buffered saline; ANOVA, analysis of variance.
Address correspondence to: Dr. Tatsuo Yamamoto, Department of Anesthesiology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260, Japan. E-mail: yamamotot{at}faculty.chiba-u.jp
|
References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Bloms-Funke P, Gillen C, Schuettler AJ, and Wnendt S (2000) Agonistic effects of the opioid buprenorphine on the nociceptin/OFQ receptor. Peptides 21: 1141-1146.[CrossRef][Medline]
Bryant RM, Olley JE, and Tyers MB (1983) Antinociceptive actions of morphine and buprenorphine given intrathecally in the conscious rat. Br J Pharmacol 78: 659-663.[Medline]
Christoph T, Kögel B, Schiene K, Méen M, De Vry J, and Friderichs E (2005) Broad analgesic profile of buprenorphine in rodent models of acute and chronic pain. Eur J Pharmacol 507: 87-98.[CrossRef][Medline]
Hammond DL, Wang H, Nakashima N, and Basbaum AI (1998) Differential effects of intrathecally administered delta and mu opioid receptor agonist on formalin-evoked nociception and on the expression of Fos-like immunoreactivity in the spinal cord of the rat. J Pharmacol Exp Ther 284: 378-387.
Huang P, Kehner GB, Cowan A, and Liu-Chen L-Y (2001) Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist. J Pharmacol Exp Ther 297: 688-695.
Hunt SP, Pini A, and Evan G (1987) Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature (Lond) 328: 632-634.[CrossRef][Medline]
Johnson RE, Fudala PJ, and Payne R (2005) Buprenorphine: considerations for pain management. J Pain Symptom Manage 29: 297-326.[CrossRef][Medline]
Kamei J, Sodeyama M, Tsuda M, Suzuki T, and Nagase H (1997) Antinociceptive effects of buprenorphine in mu1-opioid receptor deficient CXBK mice. Life Sci 60: PL333-PL337.[CrossRef]
Lutfy K, Eitan S, Bryant CD, Yang YC, Saliminejad N, Walwyn W, Kieffer BL, Takeshima H, Carroll FI, Maidment NT, et al. (2003) Buprenorphine-induced antinociception is mediated by µ-opioid receptors and compromised by concomitant activation of opioid receptor-like receptors. J Neurosci 23: 10331-10337.
Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Iwasawa Y, and Ohta H (2000) A potent and highly selective nonpeptidyl nociceptin/orphanin FQ receptor (ORL1) antagonist: J-113397. Eur J Pharmacol 387: R17-R18.[CrossRef][Medline]
Pan ZZ, Hirakawa N, and Fields HL (2000) A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin. Neuron 26: 515-522.[CrossRef][Medline]
Stevens CW and Yaksh TL (1986) Dynorphine A and related peptides administered intrathecally in the rat: a search for putative kappa opiate receptor activity. J Pharmacol Exp Ther 238: 833-838.
Wang JL, Zhu CB, Cao XD, and Wu GC (1999) Distinct effect of intracerebroventricular and intrathecal injections of nociceptin/orphanin FQ in the rat formalin test. Regul Pept 79: 159-163.[CrossRef][Medline]
Yaksh TL and Rudy TA (1976) Chronic catheterization of the spinal subarachnoid space. Physiol Behav 17: 1031-1036.[CrossRef][Medline]
Yamamoto T and Yaksh TL (1992) Comparison of the antinociceptive effects of pre- and posttreatment with intrathecal morphine and MK801, an NMDA antagonist, on the formalin test in the rat. Anesthesiology 77: 757-763.[Medline]
Yamamoto T, Nozaki-Taguchi N, and Chiba T (2002) Analgesic effect of intrathecally administered orexin-A in the rat formalin test and the rat hot-plate test. Br J Pharmacol 137: 170-176.[CrossRef][Medline]
Yamamoto T, Nozaki-Taguchi N, and Kimura S (1997) Analgesic effect of intrathecally administered nociceptin, an opioid receptor-like 1 (ORL1) receptor agonist, on the rat formalin test. Neuroscience 81: 249-254.[CrossRef][Medline]
Yamamoto T, Nozaki-Taguchi N, Sakashita Y, and Kimura S (1999) Nociceptin/orphanin FQ: role in nociceptive information processing. Prog Neurobiol 57: 527-535.[CrossRef][Medline]
Zeilhofer HU and Calo G (2003) Nociceptin/orphanin FQ and its receptor—potential targets for pain therapy. J Pharmacol Exp Ther 306: 423-429.
This article has been cited by other articles:
|
|
 |
|
  M. S. Virk, S. Arttamangkul, W. T. Birdsong, and J. T. Williams Buprenorphine Is a Weak Partial Agonist That Inhibits Opioid Receptor Desensitization J. Neurosci., June 3, 2009; 29(22): 7341 - 7348. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|
 |
 |
 |
