ognizant Communication Corporation

ANALGESIA

ABSTRACTS
VOLUME 5, NUMBER 2, 2000

Analgesia, Vol. 5, pp. 39-43, 2000
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Inflammation in the Temporomandibular Joint Region Activates Coeruleotrigeminal Modulation System in the Rat

Masayoshi Tsuruoka1 and Kiyo Matsutani2

1Department of Physiology and 2Department of Fixed Prosthodontics, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

We have compared the development of hyperalgesia during inflammation in the orofacial region between rats with bilateral lesions of the locus coeruleus (LC) and LC-intact control rats. For quantifying behavioral responses to hyperalgesia, electromyographic (EMG) activity of the masseter muscles evoked by pressure in the temporomandibular joint (TMJ) region was measured in anesthetized rats. Inflammation of the TMJ region was produced by injection of mustard oil (20 ml). Prior to mustard oil injection, the threshold of EMG activity (EMG threshold) to pressure did not differ between the LC-intact and the LC-lesioned rats. After mustard oil injection, the decreased EMG thresholds of the LC-lesioned rats were significantly lower than those of the LC-intact rats. The result suggests that the LC affects the development of hyperalgesia during inflammation in the orofacial region.

Key words: Temporomandibular joint; Locus coeruleus; Coeruleotrigeminal antinociception

Address correspondence and reprint requests to Masayoshi Tsuruoka, Ph.D., Department of Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. Tel: 81-3-3784-8160; Fax: 81-3-3784-8191; E-mail: masa@dent.showa-u.ac.jp




Analgesia, Vol. 5, pp. 45-48, 2000
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Intravenous Fosphenytoin Relieves Chronic Neuropathic Pain: A Double-Blind, Placebo-Controlled, Crossover Trial

Gary J. McCleane

Pain Clinic, Craigavon Area Hospital, Craigavon, BT63 5QQ, N. Ireland, UK

While there have been a number of studies verifying the analgesic effect of oral anticonvulsants, there have been only isolated reports of the effect of the parenteral administration of these agents in neuropathic pain. The use of intravenous phenytoin is complicated by solvent-related side effects. Fosphenytoin, a water-soluble phosphate ester pro-drug, lacks these side effects. In a blinded, placebo-controlled study of 25 patients with chronic neuropathic pain (mean duration 67 months) we compared the effect of a 24-h infusion of saline with that of 1500 PE units of fosphenytoin. Overall pain, shooting, burning, pins and needles, sensitivity, and numbness were measured using a 10-cm VAS. There were no significant changes with placebo infusion. There was a clinically and statistically significant reduction in pain scores for 18 days after fosphenytoin infusion. There were no significant changes in shooting pain, burning, sensitivity, pins and needles, or numbness. Six of the patients studied had significant reductions in their pain while the others had none. Side effects were common. It is concluded that intravenous infusion of 1500 PE units of fosphenytoin has an analgesic effect in chronic neuropathic pain and that this relief outlives both the duration of infusion and the plasma half-life of the drug.

Key words: Neuropathic pain; Fosphenytoin; Phenytoin; Anticonvulsant

Address correspondence and reprint requests to Gary J. McCleane, M.D., Pain Clinic, Craigavon Area Hospital, Craigavon, BT63 5QQ, N. Ireland, UK. Tel: 028 38 612613; Fax: 028 38 612746; E-mail: gary@mccleane.freeserve.co.uk




Analgesia, Vol. 5, pp. 49-51, 2000
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Reflex Sympathetic Dystrophy*

Heinz Konrad and Sandra M. C. M. Coeli

Pain Therapy and Palliative Care Service, Central Hospital of the Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil

We studied 30 randomly selected patients suffering from reflex sympathetic dystrophy (RSD), who have been treated and followed in our service over a period of 15 years, from January 1982 to January 1997. Our aims were: a) verify the efficacy of the therapy programs employed, b) see if there is any correlation between the studied parameters and the obtained pain reduction, and c) critically evaluate the therapy applied. We found that, regarding RSD, our service has results similar to those of other pain services throughout the world that deal with this pathology. We could not detect any correlation between the several parameters studied and the result of pain reduction. We conclude that, regarding the exact knowledge of the pathophysiology of RSD, and its resulting rational therapeutic approach, we are still almost totally in the dark.

Key words: Complex regional pain syndrome; Sympathetically maintained pain; Neuropathic pain

Address correspondence and reprint requests to Heinz Konrad, M.D., Largo Como 330, 04922-130 São Paulo, Brazil. Tel: +55 11 2474918; Fax: +55 11 55145138; E-mail: konrad@sti.com.br

*This study was published at the 9th World Congress on Pain, in Vienna, Austria, in 1999.




Analgesia, Vol. 5, pp. 53-60, 2000
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A Placebo-Controlled Study of Paroxetine and Imipramine in Human Experimental Pain Models*

Thomas P. Enggaard,1 Lars Poulsen,1 Lars Arendt-Nielsen,2 Lars F. Gram,1 and Soren H. Sindrup1

1Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense University, DK-5000 Odense C, Denmark
2Center for Sensory-Motor Interaction, Aalborg University, DK-9220 Aalborg, Denmark

Background: Clinical trials in painful diabetic neuropathy indicate that the ability of antidepressants to inhibit reuptake of serotonin and noradrenaline may be of major importance.
Purpose: This study aimed to obtain experimental evidence of the analgesic effect of a selective serotonin reuptake inhibitor (paroxetine) with a tricyclic antidepressant (imipramine) as a control.
Methods: The hypoalgesic effects of single oral doses of 40 mg paroxetine and 100 mg imipramine were evaluated in two randomized, placebo-controlled, double-blind, three-way, crossover experiments, each including 18 healthy volunteers. In Experiment I, pain tests included determination of pain detection/tolerance thresholds to pressure and pain rating during the cold pressor test. In Experiment II, pain detection/tolerance thresholds to single electric stimulation and pain summation threshold to repetitive electrical stimulation of the sural nerve were determined.
Results: Compared with placebo, imipramine significantly increased pressure pain tolerance thresholds (p = 0.03) and marginally increased thresholds for pressure pain detection (p = 0.06) and pain summation on repetitive electrical stimulation (p = 0.07). Imipramine did not cause any significant changes in pain perception during the cold pressor test or thresholds for single electrical sural nerve stimulation. Paroxetine did not alter pain perception in any of the models. Peak concentrations of paroxetine were low (30-160 nM) compared with the analgesic effective steady-state concentrations reported in clinical trials. In contrast, imipramine peak concentrations were comparable with levels found effective in clinical trials (139-441 nM).
Conclusion: The lack of effect of paroxetine in this study can be explained by low single dose drug levels but pharmacodynamic differences between paroxetine and imipramine cannot be excluded.

Key words: Paroxetine; Imipramine; Experimental pain; Human

Address correspondence and reprint requests to Thomas P. Enggaard, M.D., Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense University, Winslowparken 19, DK-5000 Odense C, Denmark. Tel: (45) 6550 3759; Fax: (45) 6591 6089; E-mail: t-enggaard@CEKFO.sdu.dk

*Preliminary results from this study were presented as a poster at the 17th Annual Meeting of American Pain Society, San Diego, November 5-8, 1998.




Analgesia, Vol. 5, pp. 61-62, 2000
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Use of Lamotrigine as a First-Line Treatment for Dysesthetic Neuropathic Pain

Jaume Canals Sotelo,1 Marc Rovira Isanta,2 Montserrat Felip,1 and Eva Barallat Gimeno3

1Palliative Care Unit, Hospital Jaume d'Urgell, Balaguer, Catalonia, Spain
2AIDS-Palliative Care Unit, Alberg St.Joan de D,u, Barcelona, Spain
3Home Care Team, Lleida, Spain

The aim of this study was to evaluate the analgesic effect of the antiepileptic drug lamotrigine as a first-line treatment in patients complaining of dysesthetic neuropathic pain, and to quantify any change in their pain scores using a visual analog scale (VAS).

Key words: Lamotrigine; Dysethetic neuropathic pain; Visual analog scale

Address correspondence and reprint requests to Dr. Jaume Canals Sotelo, Palliative Care Unit, Hospital Jaume d'Urgell, C/Urgell, 2, 25600 Balaguer, Catalonia, Spain. Tel: 973-45 03 04; Fax: 973-45 13 21; E-mail: jaume_canals@airtel.net




Analgesia, Vol. 5, pp. 63-65, 2000
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Neurolytic Block of the Ganglion Impar (Walther) in Chronic Radiation Proctitis

Edward Rabah,1 Henry Souyet,1 Carmen Aguilera,1 and Julio Elzo J2

1Department of Anesthesia and Pain Relief and 2Department of Gynecology and Oncology, Hospital San Pablo y Asociación Chilena de Seguridad, Coquimbo, Chile

Purpose: To investigate the efficacy of the neurolytic block of the ganglion impar (sympathetic) in the reduction of pain in patients with irradiated uterine cervical cancer with chronic radiation proctitis. The hypothesis is that radiation proctitis is a sympathetically mediated pain.
Methods: Eight patients were studied. The mean age was 46.8 years (range 36-57). They had been pelvic irradiated and received intracavitary radioactive implants into the uterus. They developed chronic radiation proctitis, with rectal and/or anal pain, accompanied by sensations of burning and urgency, without relief with the conventional therapy of nonopioid analgesics, opioids, tricyclic antidepressants, and adjuvant drugs (WHO ladder). All the patients were submitted to neurolytic blocks of the ganglion impar with 5 ml of 10% phenol. The pain was evaluated with VAS score: previous to the blockade, 2 h later, 24 h later, 7 days, and monthly evaluations.
Results: All the blocks were easy to perform and were confirmed by fluoroscopy without local complications. A significant reduction (p < 0.05) in VAS score 2 h after the blocks and a highly significant reduction (p < 0.001) in VAS score at 24 h, 7 days, and in all the remaining monthly evaluations were found. The mean follow-up was 11 months (range 6-17 months).
Conclusions: The neurolytic block of the ganglion impar is effective in the relief of rectal and anal pain of chronic radiation proctitis.

Key words: Neurolytic block; Sympathetic block; Ganglion impar; Ganglion of Walther; Radiation proctitis; Sympathetically mediated pain

Address correspondence and reprint requests to Dr. Edward Rabah, Chief of Department of Anesthesia and Pain Relief, Hospital San Pablo, Cordovez 540 of 304, La Serena, Chile. Fax: 56.51.324155; E-mail: rabah@entelchile.net




Analgesia, Vol. 5, pp. 67-73, 2000
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Thalamic Anteromedial and Mediodorsal Nuclei Stimulation Enhances the Self-Injury Behavior Induced by an Inflammatory Process in the Rat

Edgar Torres López, Rosendo Del Ángel, and Francisco Pellicer

Departamento de Neurofisiología, Instituto Mexicano de Psiquiatría, México

Functional brain image studies indicated that the anterior cingulate cortex is a locus for pain information process. This cortex receives projections from the anteromedial (AM) and mediodorsal (MD) thalamic nuclei through the cingulum bundle. In a previous study, we found facilitation in the onset and intensity of self-injury behavior (SIB) by simultaneous anterior cingulum bundle stimulation to the induction of a nocive regional inflammatory process. The purpose of the present work was to determine if the electrical stimulation of AM and MD nuclei of the thalamus enhances SIB. Adult Wistar male rats were stereotaxically implanted with electrodes into these nuclei and in other thalamic nuclei (OTN) (i.e., intralaminar, reticular, and stria medularis). The control groups were nonstimulated (sham) implanted and nonimplanted subjects. For the inflammatory process induction, carrageenan was injected into the hindpaw 60 min before the first stimulation trial. The severity of SIB was classified in five ranks. Results showed that all animals stimulated in AM and MD nuclei presented SIB. The AM nucleus stimulation produced a significant reduction in self-injury onset time, and the degree of self-injury behavior from AM- and MD-stimulated groups was significantly higher than those of the groups stimulated in OTN and in controls. We concluded that the AM nucleus is related with the anticipation of SIB and both AM and MD nuclei enhance the SIB induced by a nociceptive inflammatory process.

Key words: Pain; Self-injury behavior; Electric stimulation; Thalamus; Inflammation; Rat

Address correspondence and reprint requests to Francisco Pellicer, Instituto Mexicano de Psiquiatría, Camino a Xochimilco 101, San Lorenzo Huipulco, Tlalpan, México, D.F. CP: 14370. Fax: (525) 655 99 80; E-mail: pellicer@neuroserver.imp-neuro.edu.mx




Analgesia, Vol. 5, pp. 75-81, 2000
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Are m-Opioid Autoreceptors Involved in Blood Pressure and Pain Threshold Control in SHR?

Sasa Kolaric, Helena E. Makulska-Nowak, and Stanislaw W. Gumulka

Department of Pharmacodynamics and Pharmacology, Medical University, Krakowskie Przedmiescie St. 26/28, Warsaw, Poland

The aim of our study was to further investigate the paradoxical effects of intracerebroventricular (ICV) administration of very low doses of opioid antagonists on pain threshold and arterial blood pressure of spontaneously hypertensive rats (SHR) with experimental inflammation. We found that low doses of ICV administered b-funaltrexamine (0.4 mg) produced paradoxical hypoalgesia. Concomitantly, significant increases in the severity of hypertension were also observed. These results seem to confirm the engagement of the m-opioid receptor system (OP3) in the mechanisms of blood pressure control. Low doses of ICV administered naltrindole (0.3 mg) did not produce paradoxical results in either blood pressure or pain threshold. Values for these two parameters did not differ significantly from those of control SHR with experimental inflammation receiving no active treatment. Results obtained in the study suggest the involvement of the m receptor (OP3) but not the d-opioid receptor (OP1) in the paradoxical effects of opioid antagonists on pain threshold and blood pressure in SHR with experimental inflammation.

Key words: b-Funaltrexamine; Naltrindole; Paradoxical analgesia; Paradoxical hypertension; Autoreceptor theory

Address correspondence and reprint requests to Helena E. Makulska-Nowak, Krakowskie Przedmiescie St. 26/28, 00-927 Warsaw 64 #3, Poland. Tel: 828-10-88; Fax: 826-13-66.