S110 Poster Sessions / European Journal of Pain 13 (2009) S55–S285

[2] Wittmann M., Peters I, Schaaf T, et al. The effects of morphine on human

5-HT3A receptors. Anesth Analg, 2006; 103: 747–52.

362

ROLE OF GABAA- AND GABAB-RECEPTORS FOR INCISION

INDUCED PAIN BEHAVIORS

S. Reichl *, P. Zahn, E.M. Pogatzki-Zahn. Department of

Anaesthesiology and Intensive Care, University Hospital Muenster,

Muenster, Germany

There is considerable evidence that the activation of spinal GABAA-

and GABAB-receptors are involved in the neurotransmission of

inflammatory and neuropathic pain. The study assessed the role

of GABAA- and GABAB-receptor activation for incision induced

mechanical and thermal hyperalgesia.

Methods: Rats with intrathecal catheter (IT; n = 68) underwent

plantar incision and mechanical withdrawal thresholds (WT,

calibrated von Frey filaments) or thermal withdrawal latencies

(PWL, Hargreaves Box) were assessed. The animals received an

IT administration of the GABAA-agonist muscimol (0.1mg, 0.3mg),GABAB-agonist baclofen (0.1mg, 0.3mg) or vehicle and pain behavior

was evaluated again. In separate experiments animals pretreated

with the GABAA-antagonist bicuculline (0.3mg) or GABAB-antagonist

CGP35348 (30mg) received the corresponding GABAA/B-agonist.

Finally, separate animals received IT injection of bicuculline or

CGP35348 after incision.

Results: IT administration of muscimol and baclofen increased

significantly the decreased median WT after incision from 67mN to

176mN and 145mN 60–90min after injection, respectively (p < 0.05

vs. vehicle). Similar, decreased PWL after incision were increased

60–120min after agonist injection (p < 0.05 vs. vehicle). GABA-

agonist induced antinociception was blocked with pretreatment

of the corresponding antagonist (p < 0.05). IT administration of

GABAA/B-antagonist did not modify pain behaviors after incision.

Conclusion: Spinal administration of GABAA- and GABAB-agonists

decreased mechanical and thermal hyperalgesia after incision

indicating that spinal GABAA- and GABAB-receptors are potential

targets for the treatment of incisional pain and hyperalgesia.

However, because GABA-antagonists did not cause pain behaviors

in incised animals we hypothesize that tonic gabaergic inhibition

may be important for nociception after other types of tissue injuries

but not after incision.

363

DISSOCIATION OF ANALGESIC, ANTI-AVERSIVE AND REWARDING

EFFECTS OF DIFFERENT CLASSES OF ANALGESICS IN THE RAT

T. Tzschentke*, E. van der Kam, K. Rutten, A. Robens, J. De Vry.

Grunenthal GmbH, Preclinical Drug Development, Department of

Pharmacology, Aachen, Germany

Background: Morphine more potently reduces the affective as

compared to the sensory component of pain, and this effect is

not due to morphine’s rewarding properties (van der Kam et al.,

Pain 137, 373, 2008). Here we investigated whether this finding can

be generalized to other classes of analgesics.

Methods: The Randall-Selitto paw-pressure test after intraplantar

carrageenan injection was combined with conditioned place

aversion (CPA) and preference (CPP) procedures.

Results: For oxycodone (ip), the minimal-effective-dose (MED)

for producing antinociceptive effects (MEDantinoci) was 3mg/kg,

whereas the MED for anti-aversive effects (MEDanti−CPA) was

0.1mg/kg, and the MED for producing CPP in carrageenan-

treated (MEDCPP−carra) and sham-treated rats (MEDCPP−sham) was

10mg/kg and 0.3mg/kg, respectively. For pregabalin (ip),

the values were: MEDantinoci = 3mg/kg; MEDanti−CPA = 1mg/kg;

MEDCPP−carra = 3mg/kg; MEDCPP−sham = 3mg/kg. For ibuprofen (ip),

the values were: MEDantinoci = 100mg/kg; MEDanti−CPA = 3mg/kg;

MEDCPP−carra/MEDCPP−sham: no CPP up to the highest dose tested

(100mg/kg).

Conclusions: Consistent with our findings for morphine, oxycodone

showed a large dissociation of anti-aversive versus antinociceptive

effects, and of rewarding effects in animals under pain versus

controls. Ibuprofen also showed a dissociation of anti-aversive and

antinociceptive effects, but had no rewarding effects. However,

no or only a minor dissociation was found for pregabalin. This

suggests that the dissociation of rewarding effects in animals in

pain and in control animals may be limited to drugs with an opioid

mechanism of action, and that the dissociation of anti-aversive and

antinociceptive effects may not apply to all analgesic mechanisms

of action.

At the time of the study, all authors were employees of Grunenthal

GmbH.

364

THE EFFECT OF VISCERAL PAIN ON NOCICEPTIVE THRESHOLDS

OF LIMBS IN RATS

S. Vaculin*, M. Franek, R. Rokyta. Charles University, 3rd Faculty of

Medicine, Dpt. of Physiology, Prague 2, Czech Republic

Background and Aims: It is well known that acute pain

activates diffuse noxious inhibitory control (DNIC). Abnormalities

in endogenous pain inhibitory mechanisms, such as DNIC, may be

implicated in intestinal hypersensitivity in patients with irritable

bowel syndrome (IBS). Colorectal distension (CRD) in rat is used

as a model of IBS. The aim of the present study was to determine

whether CRD activates DNIC in rat.

Methods: Colorectal distension was evoked by insertion of

lubricated latex balloon into descending colon and rectum and

inflation to 80mm Hg for 10 minutes. Behavioral signs of visceral

pain were scored during the inflation together with measurements

of thermal nociceptive thresholds of limbs and tail. The thresholds

were evaluated using paw and tail withdrawal latency to thermal

stimulation using plantar test device and compared to those

obtained before the distension.

Results: Colorectal distension evoked pain behavior in all rats

(head-down position, hump-backed position, and rotation) and

increased nociceptive thresholds of forepaws, hind limbs and tail,

however, the increase of the threshold was significant only in both

hind limbs. The increase of nociceptive threshold correlated with

visceral pain score.

Conclusion: It was shown that acute visceral pain evoked

by colorectal distension in rat increases nociceptive thresholds

probably due to activation of DNIC.

Acknowledgements: The work was supported by GACR 305/07/0242

and RG 0021620816.

365

MECHANICAL HYPERALGESIA IN COX-1 And COX-2 DEFICIENT

MICE FOLLOWING CARRAGEENAN INJECTION

J. Kroin, E.Y. Chen, Y. Zhang*, A. Buvanendran, J. Kordower,

K. Tuman. Rush University Medical Center, Chicago, United States

Background: Studies in normal rodents suggest that cyclo-

oxygenase-2 (COX-2) is more important than cyclooxygenase-1

(COX-1) in the development and maintenance of inflammatory pain.

After plantar hindpaw injection of the inflammatory stimulator

carrageenan in normal rats, there is edema, hyperalgesia, and

upregulation of COX-2, but not COX-1 mRNA.

Aim: To examine if deletion of the COX-1 or COX-2 gene modifies

mechanical hyperalgesia following plantar hindpaw injection of

carrageenan.

Methods: Experiments were performed with female 129/C57Bl/6

mice (n =6/group): wild-type, COX-1 homozygous knockout (−/−),

COX-2 homozygous knockout (−/−), COX-1 deficient heterozygous

(+/−), and COX-2 deficient heterozygous (+/−). Twenty mL of 0.3%

carrageenan was injected in the left plantar hindpaw. Mechanical

hyperalgesia was assessed at 2, 4, 24, 48, and 72h post-

injection using calibrated von Frey filaments applied to the left