Presentation Number PW 095

GLYCINE MICROINJECTION INTO DPAG INDUCES HYPER AND HYPONOCICEPTION DEPENDING ON DOSE, SEX AND LOCAL OF NOCICEPTIVE STIMULUS

M. A. Martins, L. d. Bastos, C. R. Tonussi, A. d. Carobrez, Department of Pharmacology, University of Santa Catarina, Florianópolis/Santa Catarina, Brazil

Aim of Investigation: PAG stimulation produces either inhibition or facilitation of nociceptive transmission. However, it is still not clear how these mechanisms can be used in freely behaving animals. The aim of this study was to verify the effect of different levels of PAG activation on persistent nociception in superficial and deep tissue, in male and female rats.

Methods: Glycine (GLY; 10, 20 and 80 nmols / 0.3 µl) microinjection into dorsal PAG (DPAG) of Wistar male and female rats was made 5 min before formalin (2% / 50 µl) injection into knee-joint and hindpaw. Nociception was evaluated during 1 hour by the paw elevation time (PET, s) and the number of paw shaking (NS) after formalin injection, respectively.

Results: In female rats, GLY (10 and 80 nmol) microinjection into DPAG evoked hypernociception in the knee-joint test (PETPBS: 40.76 ± 4.9 s; PETGLY80: 52.00 ± 4.62 s at 25 min) and in paw test (NSPBS: 49.63 ± 8.96 s and NSGLY10: 81.56 ± 7.84 s, at 35 min). In males, GLY (10 and 20 nmols) produced hypernociceptive effect (PETPBS: 28.96 ± 3.99 s; PETGLY10: 37.08 ± 6.35 s and PETGLY20: 33.81 ± 2.63 s, at 20 min), while 80 nmols produced hyponociceptive effect (PETPBS: 47.27± 3.60 s; PETGLY80: 29.05 ± 4.64 s, at 20 min), in the knee-joint test. In the paw test, only a hypernociceptive effect with the higher dose was observed (NSPBS: 53.90 ± 6.57 s and NSGLY80: 93.50 ± 8.94 s, at 35min). Both effects, hyper and hyponociception were blocked by the co-administration of GLY with HA-966 (10 nmols / 0.3 µl) or 7-clorokynurenic acid (10 nmols / 0.3 µl).

Conclusions: It was shown here that glycine microinjection into DPAG is able to produce either facilitation or inhibition of persistent nociception, via GLY-B/NMDA site receptor. The GLY effects on PAG seem to be determined by sex and nociceptive model.

Presentation Number PW 136

SPINAL INJECTION OF FLUOROCITRATE AND MINOCYCLINE INHIBITS ARTICULAR INFLAMMATORY INCAPACITATION AND EDEMA

E. Bressan, C. R. Tonussi, Pharmacology, Federal University of Santa Catarina, Florianopolis, Brazil
Aim of Investigation: Fluorocitrate and minocycline inhibit astrocyte and microglia function, respectively. Since spinal reflexes participate in peripheral inflammation, we evaluated the potential role of spinal glia in the development of carrageenan/LPS-induced articular incapacitation, edema and leukocyte infiltration.

Methods: Inflammatory incapacitation (PET), edema, and cell migration were elicited by LPS (30 ng) injection into knee-joint, 72 hours after of the articulation priming with carrageenan (300 µg), in Wistar rats. Fluorocitrate and minocycline were intraspinally (L4-L5) delivered 20 min before LPS stimuli in a volume of 10 µl. After the 6-h period of incapacitation and edema evaluation, the animals were euthanized and the synovial fluid was sampled for mononuclear and polymorphonuclear leukocyte count.

Results: Fluorocitrate (0.3 nmol, p<0.05; 1 and 3 nmol, p<0,001) and minocycline (12, 25, 50 and 100 µg, p<0.001) produced a dose-dependent, long-lasting inhibition of articular edema. However, only the higher dose of each treatment inhibited incapacitation (PET inhibition, fluorocitrate 3 nmol: 23.18 ± 4.11 %, p<0.05; minocycline 50 µg: 17.06 ± 2.93 %, p<0.01). The higher doses of both drugs did not affect incapacitation or edema when given by intraperitoneal route. The higher of edema inhibition was observed with fluorocitrate 3 nmol (60.98 ± 14.33 %, p<0.001) and minocycline 50 µg (61,93 ± 12.94 %, p<0.001). However, edema inhibition was also observed with minor doses of each drug (fluorocitrate 1 nmol: 58.76 ± 9.85 %, p<0.001 and 0.3 nmol: 17.71 ± 9.73 %, p<0.05; minocycline 25 µg: 58.88 ± 10.93 %, p<0.001 and 12 µg: 55.55 ± 11.17 %, p<0.001). Both drugs did not affect MON and PMN migration when compared with control group.

Conclusions: These results suggest that in addition to their role in the maintenance of long-lasting nociceptive states, astrocytes and microglia may also be contributing to the development of peripheral edema. These effects seemed to be spinally-mediated, since systemic administration did not produce antiinflammatory effects. An inhibitory modulation on dorsal root reflexes is discussed as a possible explanation to the antiedematogenic effect.

Presentation Number PW 156

PHYSICAL EDUCATIONAL PROGRAM IN PATIENTS WITH CHRONIC MUSCULOSKELETAL PAIN

A. M. Maia1, V. C. Liggieri2, H. M. Yamasaki1, M. M. Gardin1, L. F. Alves1, K. R. Braga1, T. Y. Lin2, M. J. Teixeira3, 1League of Pain and Rehabilitation, Faculdade de Medicina da USP, São Paulo, Brazil, 2Division of Physical Medicine, Institute of Orthopedics and Traumatology of University of São Paulo, São Paulo, Brazil, 3Center of Pain, Faculdade de Medicina da USP, São Paulo, Brazil

Aim of Investigation: This study evaluates the functionality, quality of life, pain and kinesiophobia in patients with chronic musculoskeletal pain before and after a physical educational program.

Methods: Thirty patients (88% female, mean age: 48 years old) with chronic musculoskeletal pain were evaluated. The intensity of pain was measured by VAS, algometry for tenderness of pain were used. The quality of life was assessed using Short Form SF-36 and the fear of movement by Tampa Scale of Kinesiophobia (TSK). All underwent to 10 sessions of physical educational program consisted of ergonomic approaches, basic body anatomic and biomechanic concepts, self cares, exercises and self massage.

Results: Previous to the program, mean VAS was 6, and decreased to 2.8 (p=0.000). Health related quality of life (SF-36) was improved after the program in Physical Components (Role Physical p=0.006; Bodily Pain p= 0.019), Emotional Aspects (Role Emotional p= 0.003); Social Functioning (p= 0.002), Mental Health (p= 0.003) and no change was observed in General Health Perception (p= 0.103) and Vitality (p= 0.055). There was a significant improvement in fear of movement (p= 0.013).

Presentation Number PW 158

TREATMENT OF MYOFASCIAL PAIN SYNDROME IN PATIENTS WITH FAILED LOW BACK SYNDROME

V. C. Liggieri1, I. Luna2, A. B. Maia3, T. R. Zakka4, T. Y. Lin1, M. J. Teixeira2, 1Division of Physical Medicine, Institute of Orthopedics and Traumatology of University of São Paulo, São Paulo, Brazil, 2Pain Center Hospital das Clinicias, University of São Paulo, São Paulo, Brazil, 3League of Pain and Rehabilitation, Faculdade de Medicina da USP, São Paulo, Brazil, 4Pelvic Pain Center, Hospital da Clínicas FMUSP, São Paulo, Brazil

Aim of Investigation: Patients with failed low back pain resulted from spine surgeries usually presented severed pain and incapacity. The purpose of the study is the evaluation of the prevalence of myofascial pain syndrome (MPS) and the result of the multidisciplinary pain treatment in patients with fail back syndrome (FBS).

Methods: Thirty eight patients (68% female, mean age: 49 years old ) with chronic low back pain, after lumbar spine surgery, were evaluated. All underwent neurological, musculoskeletal and, when necessary, psychological examinations. Image and laboratorial studies were also performed. The intensity of pain was measured by VAS, algometry for tenderness of pain. The quality of life and the functionality were assessed using Short Form SF-36, Roland Morris Disability Questionaire. All underwent to physical therapy, consisted of ergonomic approaches, kinesiotherapy and dry needling of MPS.

Results: All the patients presented MPS. Almost 60% of the patients presented significant improvement of intensity of pain, functionality and QOL.

Presentation Number PW 159

MULTIDISCIPLINARY APPROACH TO MINIMIZE THE USE OF MEPERIDINE IN A PRIVATE HOSPITAL

A. C. Lopes1, F. P. Minzon2, A. C. Arantes2, F. T. Ferracine3, 1Neurology unit care, Albert Einstein Hospital, Sao Paulo, Brazil, 2Pain Management Center, Albert Einstein Hospital, Sao Paulo, Brazil, 3Pharmacy Department, Albert Einstein Hospital, Sao Paulo, Brazil

Aim of Investigation: Morphine and meperidine have been the most commonly used narcotics for the treatment of pain in hospitalized patients around the world for decades. Of these, morphine is recommended by pain experts, since it is less toxic than meperidine. The normeperidine. a metabolite of meperidine has a half-life of 14-21 hours which may be extended to 30 hours in the elderly and patients with renal insufficiency. It is a known central nervous system irritant and can cause behavioral changes such as bizarre feelings, delirium and psychosis as well as central nervous system excitation symptoms such as nervousness, myoclonus and seizures. These concerns have led the Agency for Health Care Policy and Research and the American Pain Society to make strong recommendations limiting the use of meperidine. Baseline review indicated significant inappropriate usage of meperidine at our institution. This opioid was ordered nearly twice as often as morphine. The multidisciplinary committees in the hospital made several strategies to effectively reduce meperidine usage for pain management.

Methods: We conducted a prospective study of n 3406 prescription of meperidine in Albert Einstein Hospital, Sao Paulo, Brazil, between the months of March 1, 2006 and December 31, 2007. The pharmacy's medication control system alerted to the multidisciplinary committees any meperidine order to increase institucional educations. The pharmacist follow-up of every order with the prescriber and the team suggested by phone or by a letter to the physician to adopt a guideline-based automatic opioid conversion.

Results: Throughout 22 months of study, physicians were contacted with a suggestion for an automatic opioid conversion. 87 % of the physicians who had ordered meperidine, agreed to the multidisciplinary contact and adopted hospital guideline and 23% still ordering meperidine.
The consume of meperidine decreased 24% in 2006 and 35% in 2007 in the hospital, in comparison to 2005.

Conclusions: Meperidine should be considered a second line agent in the treatment of pain when opioid analgesics are required. A pharmacist-led multidisciplinary effort resulted in a significant reduction in meperidine use at our hospital. The approach includes educational interventions as well as automatic therapeutic interchanges, that is an efficient way to optimize opioid use.

Presentation Number PW 160

MULTIDISCIPLINARY PAIN TREATMENT IN PATIENTS WITH NON VISCERAL CHRONIC PELVIC AND ABDOMINAL PAIN

T. R. Zakka1, T. Y. Lin2, A. Loduca3, A. Ungaretti Jr3, C. Samuelian3, M. J. Teixeira4, A. M. Maia5, C. Alves1, F. L. Giannella1, 1Pelvic Pain Unit, Hospital das Clínicas da FMUSP, São Paulo, Brazil, 2Divisão de Medicina Fisica e Reabilitação, Instituto de Ortopedia e Traumatologia do Hospital das Clinicas FMUSP, São Paulo, Brazil, 3Pain Center, Hospital das Clínicas da FMUSP, São Paulo, Brazil, 4Pain Center, University of São Paulo, São Paulo, Brazil, 5League of Pain and Rehabilitation, Faculdade de Medicina da USP, São Paulo, Brazil

Aim of Investigation: The purpose of the study is the results of a multidisciplinary pain treatment in patients (females were 70%) with chronic pelvic and abdominal pain (CPAP) of non visceral etiology

Methods: One hundred and twenty five patients were referred for diagnosis and treatment after previous investigation of visceral diseases (gynecological, urological or proctological disorders). Neurological, musculoskeletal and psychological and/or psychiatric evaluations were performed in all cases. Psychotropics and physical medicine procedures were prescribed to all patients. Dry needling and/or trigger point injection with local anesthetics were performed in cases that presented myofascial pain syndromes. Psychological treatment was performed when necessary.
Patients of this medical study present: age between 21y -80y;71% female - 29% male;time of pain from 6 month -21 years;time of follow-up = 1- 60 months.
Patients sometimes have difficulty to describe the pain. The terms used in this study were the McGill Pain Questionnaire. The more reported terms were: burning (49%), throbbing (29%), heavy (27%), pricking (36%), shooting (21%), and colic (7%).
Patients' functional disturbances that were observed: sleep (56.5%), humor (53.5%), leisure (63.5%), sexual (40%), appetite (40%).
Pain location: abdomen (24.3%), coccyx (6.8%), thigh-leg (10.8%), lombo-sacrum (28.4%), female genitalia (17.6%), male genitalia (6.8%), gluteal (20.3%), rectum/anus (29.7%), pelvis (52.7%).
Associated disorders: surgical procedures (45.6%), endometriosis (4.5%), fibriomyalgia (9.1%), peripheric neuropathy, trauma (5.7%), no diseases (18.2%)

Results: Myofascial pain syndrome of the pelvic floor and gluteus muscles was diagnosed in all patients. In 22.6% of the cases, there were also neuropathic abnormalities. The multidisciplinary treatments resulted in significant improvement of pain and quality of life in 65.2% of the patients

Conclusions: Myofascial pain syndrome and peripheral neuropathies can be source of non visceral CPAP. The appropriate diagnosis and treatment of CPAP are very important to improve the pain and also the quality of life of these patients

Presentation Number PW 315

THE MOLECULAR MECHANISM OF PERIPHERAL ANTINOCICEPTIVE ACTION OF MORPHINE: ACTIVATION OF PI3K-GAMMA-AKT-NITRIC OXIDE SIGNALING PATHWAY

T. M. Cunha1, C. M. Lotufo1, M. I. Funez1, A. C. Domingues1, W. A. Verri Jr1, M. M. Teixeira2, J. S. Hothersall1, F. Q. Cunha1, S. H. Ferreira1, 1Pharmacology, University of Sao Paulo-FMRP, Ribeirao Preto, Brazil, 2Department of Biochemistry and Imunology, Institute of Bilogical Science (ICB),, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

Aim of Investigation: The increased intensity of nociception during inflammation (hypernociception) is primary due to the sensitization of specific classes of nociceptive neurons. Morphine directly blocks hypernociception via the activation of nitric oxide/cGMP/PKG/K+(ATP) channels signaling pathway. In the present study we tested whether the initiation of this signaling cascade depends on the stimulation of the PI3Kγ/AKT.

Methods: Mechanical hypernociception was evaluated in PGE2 sensitized paws of rats and mice using a modification of the Randall-Sellito test and an electronic version of the von Frey test, respectively. The expression of mu-opioid receptors, PI3Kγ and TRPV1 in dorsal root ganglion (DRG) neurons was detected by immunofluorescense (confocal microcopy). Phosphorylated AKT expression was analyzed by western blot of DRG culture neurons. Nitric oxide production by DRG neurons was evaluated using fluorescent DAF indicator (confocal).

Results: Confocal analysis showed that PI3Kγ is expressed in DRG neurons, mainly in neurons of small size, which also express TRPV1 and mu-opioid receptor. PI3Kγ is also expressed in IB4 positive neurons. Non-selective (wortmannin, 1-10 μg/paw) or selective (AS 605240, 10-90 μg/paw) pharmacological inhibition of PI3Kγ prevented in rats the peripheral anti-hypernociceptive action of morphine (6 μg/paw) or DAMGO (1 μg/paw). In PI3Kγ-deficient mice (-/-), morphine as well as DAMGO did not show a peripheral anti-hypernociceptive effect. Further investigation of the PI3Kγ downstream signaling pathway showed that the AKT-selective inhibitor (3-30 mg/paw) also prevents morphine and DAMGO anti-hypernociceptive effects. Corroborating with this in vivo observation, the incubation of DRG culture neurons with morphine (10 μM) or DAMGO (1 μM) increases the phosphorylation of AKT. This activation was prevented by naloxone (10 μM) and PI3Kγ inhibitor (AS 605240; 1 μM) and was found to be reduced in cultured neurons of PI3Kγ (-/-). Incubation of DGR neurons with morphine induced an increase of nitric oxide production that was inhibited by PI3Kγ and AKT inhibitors.

Conclusions: The present results suggest that the peripheral blockade of hypernociception by morphine seems to be dependent on m-opioid receptor, with an initial activation of the PI3Kγ/AKT signaling pathway, which is ultimately responsible for the activation of the nitric oxide/cGMP/PKG/K+(ATP) channel pathway.

Presentation Number PW 318

THE IMPORTANCE OF PRIMARY AFFERENT NEURONS IN THE SYNTHESIS OF PROSTAGLANDINS INVOLVED IN INFLAMMATORY HYPERALGESIA

C. A. Parada1,2, D. Araldi2, L. F. Ferrari2, C. C. Lotufo2, S. H. Ferreira2, 1Physiology and Biophisics, University of Campinas UNICAMP, Campinas, Brazil, 2Pharmacology, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, Brazil

Aim of Investigation: To verify whether the activation of neuronal COX-1 or COX-2 and the synthesis of prostaglandins by primary afferent neurons contribute to the development of inflammatory hyperalgesia in peripheral tissue.

Methods: Mechanical nociceptive thresholds were measured using an electronic von-Frey. IL-1 beta was administrated in the subcutaneous tissue of the rat hind paw. Indomethacin or selective inhibitors of COX-1 (valeryl salicylate; 3-30 mg) or COX-2 (SC236; 30-300 mg) or oligodeoxynucleotides (ODN) antisense specifically designed against both isoforms of COX (20 mg per day for 4 days) were directly administered into the ipsilateral L5 dorsal root ganglion (DRG) of rats (J Neurosci Methods 2007;159:236-43). Expressions of COX-1 or COX-2 in the DRG L5 were quantified by immunofluorescence and/or Western blot.

Results: Indomethacin or SC236 administrated in the DRG L5 completely prevented the mechanical hyperalgesia induced by IL-1 beta in the rat hind paw, while valeryl salicylate significantly reduced it (68%). ODN antisense, but not mismatch, against COX-1 or COX-2 specifically decreased their expressions in the DRG (50% and 30%, respectively)and significantly reduced the IL-1-beta-induced hyperalgesia (65% and 78%, respectively). This study also demonstrated that IL-1 beta administered into the subcutaneous tissue of the hind paw significantly increased the COX-2 expression in TRPV-1 neurons of DRG and that both COX isoforms, COX-1 and COX-2 are constitutively expressed in primary afferent neurons.

Conclusion: The activation of COX-2 in primary afferent neurons is important to the development of inflammatory hyperalgesia.

Presentation Number PW 329

EFFECT OF PREEMPTIVE ACUPUNCTURE ON THE C-FOS EXPRESSION INDUCED BY PAW INCISION SURGERY IN THE SPINAL CORD OF WISTAR RATS

M. B. Henao1, L. Lemonica1, M. A. Medeiros2, G. A. Barros1, 1Anesthesiology, Botucatu Medical School - UNESP, Botucatu - SP, Brazil, 2Animal Physiology, Rio de Janeiro Federal University, Rio de Janeiro - RJ, Brazil

Aim of Investigation: To measure the effect of acupuncture on the expression of c-Fos in the dorsal horn of spinal cord after noxious stimuli induced by paw incision in rats.

Methods: 42 male Wistar rats that received surgical paw incision under sodium thiopental anesthesia were divided in two groups: presurgery (G1) or postsurgery (G2), according to whether acupuncture was performed before or after the surgery. Each group was divided into three subgroups: control (CT, no stimulation), manual acupuncture at acupoints *shen* (kidney 1), *shiyin* (bladder 67) and *zusanli* (stomach 36) (MA, only needles, without any other stimulation), and electrical acupuncture (EA, same acupoint with electrical current of 100 Hz). The acupuncture was performed for 20 minutes. One hour after the final stimulus (surgery for G1 and acupuncture for G2), the animals were perfused and c-Fos expression was assessed immunohistochemically (ab-5, Oncogene). The number of c-Fos-immunoreactive cells was counted at the dorsal horn at the L5 vertebral level, and the results are reported as number of c-Fos-immunoreactive cells/10,000 µm2.

Results: We did not find changes in the c-Fos expression between the different treatments: F=0.22; p>0.10 (CT(4.05)=MA(12.23)=EA(13.38)). Similarly, we did not find differences in c-Fos expression between the groups: F=1.14; p>0.10(pre=post). Given the similar c-Fos expression in all animals, we conclude that the treatments were not effective, although there was a tendency for increased c-Fos expression in the animals of the acupuncture-treated group, as compared to the control group.

Conclusions: Acupuncture analgesia (MA and EA) as applied here was not effective in altering the noxious stimulus-induced c-Fos expression in the dorsal horn of the spinal cord.

Presentation Number PW 346

THE USE OF TOPICAL ANALGESICS AS ADJUVANTS IN THE TREATMENT OF CHRONIC PAIN PATIENTS

T. Y. Lin1, A. M. Maia2, T. R. Zakka3, M. J. Teixeira4, H. M. Yamazaki1, M. M. Gardin1, V. C. Liggieri5, K. R. Braga2, 1Pain Clinic, Institute of Orthopedics and Traumatology, University of Sao Paulo, São Paulo, Brazil, 2League of Pain and Rehabilitation, University of São Paulo, São Paulo, Brazil, 3Pelvic Pain Unit, Hospital das Clinicas FMUSP, São Paulo, Brazil, 4Pain Center, Hospital das Clinicas, University of Sao Paulo, São Paulo, Brazil, 5Division of Physical Medicine, Institute of Orthopedics and Traumatology, University of Sao Paulo, São Paulo, Brazil

Aim of Investigation: To evaluate the analgesic effects of a topical formulation composed by amitriptiline 3%, lidocaine 7% and transdermal gel PLO, in patients with chronic musculoskeletal and or neuropathic pain. In those without allergy, mentol 4% and camphore 3% were also used.

Methods: A hundred and fifty patients (70.3% female; mean of the ages: 52.9 years) with severe chronic pain (mean duration of pain: 47.3 months) were evaluated. All underwent to neurological, musculoskeletal and, when necessary, psychological examinations. Image and laboratorial studies were also performed. The diagnosis of pain was myofascial pain syndrome (MPS) in 67.8% of the patients; fibromyalgia in 15.6%; neuropathic pain (NP) in 11.1%; MPS associated with NP in 5.5%. VAS was used to evaluate the intensity of pain. The analgesic effect was considered as good when the improvement was more than 50% of the pain, and poor, when less than 50%.

Results: Prior to the use of analgesics formulation, the VAS was 7.8, and decreased to 2.9 immediately after the use. The results were considered as good in 64.9% of the patients and poor in 35.1%. The analgesic effect of the formulation lasted from 4 to 8 hours (mean of 4.5 hours). Few patients presented drowsiness, dry mouth and or contact allergy. The mean duration of follow-up period was 9.7 months.

Presentation Number PH 011

EFECTS DETERMINED BY THE ADMINISTRATION OF PRESERVATIVE-FREE S(+)-KETAMINE ON THE SPINAL CORD AND THE MENINGES. EXPERIMENTAL STUDY IN DOGS

J. G. Alves1, A. Rojas1, G. A. Barros1, M. E. Marques2, L. A. Vane1, E. M. Ganem1, 1Anesthesiology, Botucatu Medical School - UNESP, Botucatu - SP, Brazil, 2Pathology, Botucatu Medical School - UNESP, Botucatu - SP, Brazil

Aim of Investigation: Ketamine and its active enantiomer S(+)-ketamine (SK), both N-methyl-D-aspartate receptor antagonists, have been administered by epidural and intrathecal routes for the treatment of acute perioperative pain and to provide adequate relief in neuropathic pain syndromes. In rabbits, the repeated intrathecal administration of preservative-free SK resulted in toxicity on the central nervous system. This study aims to investigate whether preservative-free SK (50 mg/ml) injected in a single dose would be toxic over the spine and meninges of dogs.

Methods: After approval of the Committee on Ethical Animal Research of the institution, sixteen dogs were randomly assigned in two groups: G1 (control, 0.9% saline solution) and G2 (SK, 1 mg/kg). Intrathecal puncture was performed in L6-7 interspace. In both groups the total volume injected was 1 ml over a period of 10 seconds. The animals were submitted to sensory and motor neurological evaluation every day during a period of 21 days. After this period they were sacrificed and the spinal cord, cauda equina roots, and meninges were removed for histologic light microscopy.

Results: None of the G1 and G2 animals presented any clinical or histological changes in the spinal cord or meninges.

Conclusions: In this experimental model a single intrathecal injection of SK (1 mg/kg) did not determine any clinical changes during the evaluation period and did not induce any histological injury on light microscopy.

Presentation Number PH 016

EFECTS OF THE INTRATHECAL ADMINISTRATION OF METHYLPREDNISOLONE ON THE SPINAL CORD AND THE MENINGES. EXPERIMENTAL STUDY IN DOGS

R. M. Lima1, G. A. Barros1, M. E. Marques2, L. H. Lima1, N. S. Modolo1, A. D. Pimenta1, L. A. Vane1, E. M. Ganem1, 1Anesthesiology, Botucatu Medical School - UNESP, Botucatu - SP, Brazil, 2Pathology, Botucatu Medical School - UNESP, Botucatu - SP, Brazil

Aim of Investigation: Methylprednisolone is one of the most used steroids, injected via the epidural route, in the treatment of the low back pain. Although its use is controversial in the current literature, it still very often used worldwide. The inadequate injection of this medication into the intrathecal space is related to the occurrence of adhesive arachnoiditis. Based on this information, possible clinical and histological alterations caused by methylprednisolone, a potent depo-corticosteroid, administered into the intrathecal space of dogs were evaluated.

Methods: Fourteen dogs were randomly and blindly assigned to two study groups: Group 1 - 0.9% saline solution, 1 ml, and Group 2 - Methylprednisolone 1.15 mg/kg, 1 ml. All the animals were clinically evaluated for 21 days, and then were sacrificed by electroshock with penthobarbital anesthesia. The lumbar and sacral portions of the spinal cord were removed for histological analyses, under light microscopy.

Results: In Group 1, none of the animals presented clinical or histological alterations. Histological alterations were observed in all the animals of Group 2; six animals presented normal nerve tissue and one demonstrated necrosis in the dorsal part of the spinal cord. The main histological alterations found in Group 2 were areas of thickness in the meninges and in the blood vessels and lymphoplasmocytic inflammatory infiltration. In three animals of Group 2, adherences were found in the pia mater, arachnoid and dura mater meninges, and nerve roots enclosed by fibrosis. All the animals were clinically normal.

Conclusions: The intrathecal administration of methylprednisolone determines histological changes in the spinal cord and meninges of dogs in this study model.

Presentation Number PH 019

IMMEDIATE NOCICEPTION AND LONG-LASTING THERMAL HYPERPATHIA INDUCED BY PGE2 INTRAPLANTAR INJECTION IN RATS: TWO NEW NOCICEPTIVE PARAMETERS IN PATHOLOGICAL STATES

L. C. Bastos, C. R. Tonussi, Pharmacology, Federal University of Santa Catarina, Florianópolis, Brazil

Aim of Investigation: : Besides its well-studied hypernociceptive effect, we recently observed that intra-plantar (i.pl.) injection of PGE2 also evokes immediate nociception (Toxicon 43:273, 2004) and a long-lasting state of thermal hyperpathia. In this work we investigated the role of COX, histamine, and serotonin on these nociceptive parameters.

Methods: Male Wistar rats received a 50 µl (i.pl.) injection of PGE2 (350 ng/paw), and i.p. pretreatments with loratadine (10 mg/kg), indomethacin (2.5 mg/kg), methysergide (5 mg/kg v.o) before i.pl. injection, or PGE2 associated with indomethacin (17.5; 35; 70 nmol), methysergide (0.5; 1; 2 nmol), cyproheptadine (0.16; 0.5; 1.5 pmol), NAN-190 (0.05; 0.1; 0.2 pmol), and ondansetron (0.065; 0.13; 0.26 pmol). The nocifensive behaviour was scored by the paw’s shaking, lifting, and licking movements (NSL) during 5 min, just after the i.pl. injection and hourly (1-6 h), just after paw immersion in hot water (50 °C/7s). The Hargreaves test was used for detecting the lowering of thermal threshold after PGE2 (350 ng/paw) and carrageenan (500 µg/paw) treatment.

Results: Systemic treatment with loratadine, indomethacin, and methysergide and local treatment with cyproheptadine inhibited immediate nociception (p<0.05). Hyperpathia was inhibited by systemic treatment with indomethacin or methysergide (p<0.001), and also by local treatment with indomethacin (p<0.01), methysergide, cyproheptadine, NAN-190, and ondansetron (p<0.001). Nevertheless, methysergide (0.5 nmol) increased hyperpathia (p<0.05). PGE2 did not lower thermal threshold in the Hargreaves test.

Conclusions: Immediate nociception is not direct, but mediated by COX and also by histamine H1 and serotonin 5-HT2 receptor activation. The hyperpathia is mediated by COX and serotonin receptors (5-HT1A, 5-HT2, 5-HT3), although some peripheral inhibitory serotonin receptor may be involved.

Presentation Number PH 039

PAIN MANAGEMENT IN THE NEONATAL INTENSIVE CARE UNIT

E. A. Bussotti1, E. R. Leão2, 1Neonatal Intensive Care Unit, Hospital Samaritano, São Paulo, Brazil, 2Scientific Research Department, Hospital Samaritano, São Paulo, Brazil

Aim of Investigation: To characterize the painful procedures performed by the nursing team in the neonatal intensive care unit (NICU) and to verify the pain management techniques used.

Methods: This descriptive and exploratory study was conducted in a private hospital in the city of São Paulo, Brazil. All neonates hospitalized were examined in the last quarter of 2007. The sample was characterized according to gestation age at birth, clinical specialty, and length of stay in the NICU. The painful procedures were identified, counted, and characterized according to type and pain intensity. Pain was assessed using the Neonatal Infant Pain Scale (NIPS) and was classified according to the type of therapy: pharmacological therapy (PT), nonpharmacological therapy (NPT), both pharmacological and nonpharmacological therapy (PNPT), and no therapy (NT).

Results: Subjects included in this study were 35 neonates, 31 (88%) with gestationa