Use of a pulsed electromagnetic field for treatment of post-operative pain in dogs: a pilot study

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1 Veterinary Anaesthesia and Analgesia, 2002, 29, 43^48 RESEARCH PAPER Use of a pulsed electromagnetic field for treatment of post-operative pain in dogs: a pilot study Heidi L Sha ord DVM, Peter W Hellyer DVM, MS, Dipl ACVA, KennethTCrump CVT, Ann E Wagner DVM, MS, Dipl ACVA, Khursheed RMama DVM, MS, Dipl ACVA &JamesSGaynor DVM, MS, Dipl ACVA Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, USA Correspondence: Peter Hellyer, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. Abstract Objective To determine if pulsed electromagnetic eld (PEMF) therapy reduces post-operative pain in dogs following ovariohysterectomy, and to evaluate PEMF interaction with post-operative morphine analgesia. Study design Randomized controlled clinical trail. Animals Sixteen healthy dogs weighing 18 (10^32) kg [median (range)] and aged13 (3^36) months. Materials and methods Anesthesia consisted of atropine (0.04 mg kg 1, SC), acepromazine (0.02 mg kg 1, SC), fentanyl (0.0 1mg kg 1, SC), thiopental (10^15 mg kg 1, IV) and halothane in oxygen. Ovariohysterectomies were performed by senior veterinary students. Pain score (numeric rating scale, 0^28), pulse rate, respiratory rate, indirect mean arterial pressure (MAP), and body temperature were evaluated prior to anesthetic premedication, at extubation,30minutes after extubation, and then hourly for 6 hours. Following extubation, dogs were randomly divided into four groups: a control group that received 0.9% NaCl, IV, and no PEMF; a magnet group that received 0.9% NaCl, IV, and PEMF; a morphine group that received morphine 0.25 mg kg 1, IV, and no PEMF; and, a magnet/morphine group that received morphine 0.25 mg kg 1,IV,andPEMF.A single observer, blinded to treatment, obtained all behavioral observations and physiologic data. Data were analyzed using the Kruskal^Wallis statistical test with a signi cance of p < Results Signi cant di erences in MAP (mm Hg) [median (range)] occurred at 300 minutes [morphine 108 (83^114) and magnet/morphine 90 (83^97) < magnet135 (113^117)], and at 360minutes [magnet/morphine 93 (81^100) < control 127 (111^129) and magnet 126 (111^129)]. At 30minutes the total pain score for the magnet/morphine group [1.5 (0^5)] was signi cantly less than control [8 (6^13)], but not di erent from magnet [5.5 (4^7)] or morphine [4.5 (2^9)]. Conclusions and clinical relevance Although no clear bene t was seen in this study, the results suggest that PEMF may augment morphine analgesia following ovariohysterectomy in dogs, and that further study of the analgesic e ects of PEMF is warranted. Keywords analgesia, pulsed electromagnetic eld. Introduction Interest in the therapeutic use of electromagnetic elds has grown over the past two decades since pulsed electromagnetic eld (PEMF) therapy gained Food and Drug Administration (USA) approval for the treatment of human patients with nonunion fractures and congenital pseudoarthrosis (Bassett 1993). Use of PEMF has been incorporated into the treatment of tendinitis in both humans (Binder et al. 1984) and horses (Auer et al.1983). In addition, PEMF has been shown to enhance wound healing in the dog (Scardino et al. 1998). Relief from chronic pain has been a common nding associated with PEMF 43

2 treatment in human patients (Binder et al.1984; Ellis 1993,Trock et al. 1994), however, PEMF therapy does not appear to provide analgesia in acute pain models (Kavaliers & Ossenkopp1985; Reed etal.1987). No studies have investigated PEMF-mediated pain relief in animals. The objective of this pilot study was to obtain preliminary information evaluating the analgesic e ects of PEMF in dogs. Speci cally, we investigated the ability of a therapeutic PEMF to control post-operative pain, and evaluated its interaction with post-operative morphine analgesia in dogs undergoing routine ovariohysterectomy. Materials and methods Animals Sixteen intact, nongravid female dogs weighing 18 (10^32) kg [median (range)] and aged 13 (3^36) months were the subjects of this pilot study. They were presented to the Colorado State University Veterinary Teaching Hospital by the Larimer County Humane Society for elective ovariohysterectomy. The Colorado State University Animal Care and Use Committee approved the use of dogs in this study. All dogs were determined to be in good health based upon physical examination ndings, packed cell volume, and total plasma protein concentration determined the day before surgery. Procedures Dogs were acclimated to a large cage overnight. Food, but not water, was withheld for 12 hours prior to the start of anesthesia. The magnetic eld unit (Magnavet, Integra Animal Health, Moraga, CA, USA) was hung on the cage but was not turned on. On the morning of surgery, prior to administration of anesthetic premedications, baseline pulse rate (HR), respiratory rate (RR), rectal temperature (T), indirect mean arterial blood pressure (MAP) (Dinamap, Criticon Inc.,Tampa, FL, USA), cumulative pain score (Appendix A), and behavioral observations of each dog were obtained. Thirty minutes after administration of anesthetic premedications (atropine 0.04 mg kg 1, SC, acepromazine 0.02 mg kg 1,SC,andfentanyl0.01mgkg 1, SC), an IV catheter was placed in a peripheral vein and anesthesia was induced with thiopental to e ect (10^15 mg kg 1, IV). Following endotracheal intubation, anesthesia was maintained with halothane in 100% oxygen. Crystalloid uids (Lactated Ringer s Solution, Abbott Laboratories, North Chicago, IL, USA) were administered IV at a rate of 10mL kg 1 hour 1 for the duration of surgery. Standard ovariohysterectomies were performed by senior veterinary students under direct supervision of a faculty member. Total time of anesthesia and surgery were recorded. Dogs were returned to their cages for recovery and observation. At the time of extubation, dogs were randomly assigned to one of four treatment groups with four dogs per group. Control dogs received 0.9% NaCl, IV, and no PEMF treatment post-operatively. Dogs in the magnet group received both 0.9% NaCl, IV, and PEMF treatment. Dogs in the morphine group received morphine 0.25 mg kg 1,IV,andnoPEMF treatment. The group of magnet/morphine dogs received both morphine 0.25 mg kg 1,IV,andPEMF treatment. The dose of morphine was chosen to provide analgesia while minimizing post-operative sedation to prevent interference with subsequent behavioral assessments.the morphine was administered intravenously to avoid variability in absorption and onset of action. A single observer (KC), blinded to the treatment administered, made all of the behavioral observations during the 6-hour recovery period. Pulse rate, respiratory rate, rectal temperature, indirect mean arterial blood pressure, cumulative pain score and behavioral observations were obtained at the time of extubation (T ¼ 0), and at 30,60,120,180,240,30 0 and 360minutes after extubation. Pulsed electromagnetic eld treatment The magnetic eld unit was attached to the outside of the cage and the magnetic eld was measured using a tri eld gaussmeter and con rmed to be within the cage. The magnetic eld unit delivered a pulsed electromagnetic eld at 0.5 Hz for alternating periods of 20minutes on and 20minutes o for the 6-hour recovery period. The pulsed electromagnetic eld con guration was recommended by the manufacturer for relief of pain in animals (Peppin 1998). Control and morphine dogs were exposed to a nonfunctional, though visibly identical, electromagnetic eld unit during the recovery period. Evaluation of pain Nine di erent criteria re ecting behavioral and physiologic responses to pain were evaluated to determine the cumulative pain score (Appendix A). 44 Veterinary Anaesthesia and Analgesia, 2002, 29, 43^48

3 Criteria included comfort, movement, appearance, unprovoked behavior, interactive behavior, vocalization, heart rate, respiratory rate and mean arterial pressure. Dogs were observed for approximately 10minutes at each data collection point. Any dog exhibiting excessive pain, de ned as a cumulative pain score of 17, was administered morphine (0.5 mg kg 1, IV) immediately, and removed from further study. Statistical analysis Data were analyzed using the Kruskal^Wallis oneway analysis of variance test with a signi cance of p <0.05 (Sheskin 1997). Where signi cant di erences were detected with Kruskal^Wallis analysis, Sche e s post-hoc test was performed to determine where differences between groups existed. All data are presented as medians, with range in parentheses. Results Baseline values for HR, RR, temperature, MAP and cumulative pain score were not signi cantly different between groups. Heart rate [111 (80^150) beats minute 1 ], RR [30(16^80) breaths minute 1 ], and temperature [101.98F (100^103.2)] were not signi cantly di erent between groups at any time. The median length of anesthesia and surgery for all groups was 143 (100^200) minutes, and 89 (45^ 130) minutes, respectively, and these variables did not di er signi cantly between groups. At T ¼ 300 both morphine MAP [108 (83^114) mm Hg] and magnet/morphine MAP [90(83^97) mm Hg] were signi cantly less than the magnet MAP[135(113^117)mmHg](Table1).AtT¼ 360 magnet/morphine MAP [93 (81^100) mm Hg] was signi cantly less than both the control MAP [127 (111^129) mm Hg] and magnet MAP [126 (111^129) mm Hg]. Cumulative pain scores (Table 2) tended to reach a maximum at the time of extubation (T ¼ 0 ) or T ¼ 30, and then decrease over time for all treatments. At T ¼ 30the cumulative pain score for the morphine/magnet group [1.5 (0^5)] was signi cantly less than control [8 (6^13)], but was not di erent from magnet [5.5 (4^7)], or morphine [4.5 (2^9)]. Two dogs in the control group exhibited excessive pain and were administered additional analgesia, one at T ¼ 180and the second at T ¼ 360. Data collected from these two animals are included up to the point where they received additional analgesia. Table 1 Mean arterial pressure (mm Hg) presented as median (range) obtained from16 dogs following elective ovariohysterectomy. Post-operatively the control group received 0.9% NaCl, IV and no pulsed electromagnetic eld (PEMF); the magnet group received 0.9% NaCl, IV, and PEMF; the morphine group received morphine 0.25 mg kg 1, IV, and no PEMF; the magnet/morphine group received morphine 0.25 mg kg 1,IV,andPEMF.N ¼ 4forallgroups. Group Baseline T ¼ 0 30 minutes 60 minutes 120 minutes 180 minutes 240 minutes 300 minutes 360 minutes Control (60 128) (86 107) (87 114) ( ) ( ) (65 123) ( ) ( ) ( ) Magnet (60 128) (86 107) (87 114) ( ) ( ) (65 123) ( ) ( ) ( ) Morphine y 108 (46 113) (85 98) (93 111) (93 111) (77 117) (82 111) (93 129) (83 114) ( ) Magnet/ y 93 y Morphine (89 100) (73 117) (65 109) (67 110) (86 121) (62 98) (62 101) (83 97) (81 100) Indirect MAP obtained prior to surgery (baseline), at extubation (T ¼ 0), 30 minutes after extubation, and then hourly for 6 hours. Significantly different from control group (p < 0.05). ysignificantly different from magnet group (p < 0.05). Veterinary Anaesthesia and Analgesia, 2002, 29, 43^48 45

4 Table 2 Cumulative pain scores obtained from 16 dogs following elective ovariohysterectomy presented as median (range). A 28-point scale evaluating comfort, movement, appearance, unprovoked and interactive behaviors, vocalization, heart rate, respiratory rate, and MAP was used to determine the cumulative pain score (Appendix A) Group Baseline T ¼ 0 30 minutes 60 minutes 120 minutes 180 minutes 240 minutes 300 minutes 360 minutes Control (1 3) (6 14) (6 13) (3 11) (3 14) (4 17) (2 13) (3 12) (1 14) Magnet (1 3) (4 7) (4 7) (1 7) (2 4) (1 8) (2 6) (0 7) (1 7) Morphine (1 2) (8 10) (2 9) (1 12) (2 12) (1 10) (2 9) (1 11) (1 6) Magnet/ Morphine (1 2) (2 11) (0 5) (1 5) (1 5) (2 4) (2 3) (0 3) (1 2) Significantly different from control group (p < 0.05). The following behavioral observations were made of each group. Control group: one dog retched/vomited at T ¼ 30and T ¼ 180; another dog would not lie downatt ¼ 30; a third dog who appeared uncomfortable throughout the study, but did not receive a total pain score >17 at any observation point, was administered morphine at T ¼ 360; and the fourth dog was salivating at T ¼ 180, had a pain score of 17 and was administered morphine at that time. Magnet group: one dog vomited three times during a walk at T ¼ 240. Morphine group: one dog did not want to lie down at T ¼ 180or T ¼ 300; another dog was noted to be looking at its incision site at T ¼ 0, 30, 60, 120, 240 and 300. Magnet/morphine group: one dog vocalized at the time of extubation, T ¼ 180and T ¼ 300, and it was noted that whining occurred when this dog was ignored. Discussion In this pilot study, we found that PEMFcontributed to post-operative analgesia in dogs undergoing elective ovariohysterectomy. The MAP of both the morphine and morphine/magnet groups tended to return towards baseline values by T ¼ 300, whereas that of the control and magnet groups tended to increase. Sammarco et al. (1996) reported a similar trend of post-operative MAP increasing over time in a control group of dogs. Although morphine analgesia and sedation were expected to have diminished by T ¼ 300, dogs receiving morphine may have experienced greater analgesia and sedation, and decreased endogenous catecholamine release throughout the study, all of which could have contributed to lower MAP than dogs not receiving morphine. As found in a previous study, MAP, heart rate and respiratory rate did not appear to correlate with behavioral indicationsofpain(conzemiusetal.1997).painscoresfor all groups tended to be greatest at the time of extubation. Post-anesthetic delirium may have contributed to high scores at this time. The pain scores of control dogs tended to be greater than all other groups for the rst 180minutes. Lascelles et al. (1997) reported a similar trend in pain scores of control dogs following ovariohysterectomy. In this study, the magnet group tended to have lower pain scores than the control and morphine groups during the rst 180minutes following extubation. It is possible that PEMF potentiation of morphine analgesia contributed to the nding that morphine/magnet pain scores were signi cantly less than control at T ¼ 30. Our results suggest that exposure to a PEMF does not interfere 46 Veterinary Anaesthesia and Analgesia, 2002, 29, 43^48

5 with morphine analgesia, unlike a previous study which found that exposure to a rotating magnetic eld, not a PEMF, inhibited morphine analgesia in rats (Kavaliers & Ossenkopp1985). Ovariohysterectomy has been used by other investigators as a standardized model of surgical pain (Lascelles et al. 1997, 1998) and for description of post-operative behavioral parameters in dogs (Hardie et al. 1997). We used both objective (MAP, HR, RR) and subjective (behavioral observation) measures to help determine the severity of post-operative pain. We tried to minimize observer variability by having a single person obtain all pain score data. The behavioral comments o er insight into individual animal responses to treatments and suggest that all dogs in the control group were uncomfortable. Quantitative behavioral measurements may have detected more subtle di erences between groups and are recommended for future studies of PEMF-mediated analgesia. PEMF therapy has proven successful in the treatment of pain associated with chronic tendinitis and osteoarthritis in people (Binder et al. 1984; Trock et al. 1994). Results of this pilot study suggest that PEMF may mediate acute post-surgical pain relief and that further research on clinical application and mechanisms of action is warranted. References Auer JA, Burch GE, Hall P (1983) Review of pulsing electromagnetic eld therapy and its possible application to horses. EquineVet J15,354^360. Bassett CAL (1993) Bene cial e ects of electromagnetic elds. J Cell Biochem 51,387^393. Binder A, Parr G, Hazleman B et al. (1984) Pulsed electromagnetic eld therapy on persistent rotator cu tendinitis. Lancet1,695^698. Conzemius MG, Hill CM, Sammarco JL et al. (1997) Correlation between subjective and objective measures used to determine severity of postoperative pain in dogs. J AmVet Med Assoc 210, 1619^1622. Ellis WV (1993) Pain control using high-intensity pulsed magnetic stimulation. Bioelectromagnetics 14, 553^556. Hardie EM, Hansen BD, Carroll GS (1997) Behavior after ovariohysterectomy: what s normal? Appl Anim Behav Sci 51,111^128. Kavaliers M, Ossenkopp KP (1985) Exposure to rotating magnetic elds alters morphine-induced behavioral responses in two strains of mice. Neuropharmacology 24, 337^340. Lascelles BDX, Cripps PJ, Jones A et al. (1997) Post-operative central hypersensitivity and pain: the pre-emptive value of pethidine for ovariohysterectomy. Pain 73, 461^471. Lascelles BDX, Cripps PJ, Jones A et al. (1998) E cacy and kinetics of carprofen, administered preoperatively or postoperatively, for the prevention of pain in dogs undergoing ovariohysterectomy.vet Surg 27,568^582. Peppin B (1998) Marketing product manager. Integra Animal Health, Moraga, CA.Telephone consultation with PW Hellyer. Reed MW, Bickersta DR, Hayne CR et al. (1987) Pain relief after inguinal herniorrhaphy. Ine ectiveness of pulsed electromagnetic energy. Br J Clin Pract 41,782^784. Sammarco JL, Conzemius MG, Perkowski SZ et al. (1996) Postoperative analgesia for sti e surgery: a comparison of bupivacaine, morphine or saline.vet Surg 25,59^69. Scardino MS, Swaim SF, Sartin EA et al. (1998) Evaluation of treatment with a pulsed electromagnetic eld on wound healing, clinicopathologic variables, and central nervous system activity in dogs. Am J Vet Res 59,1177^1181. Sheskin DJ (1997) Handbook of Parametric and Nonparametric Statistical Procedures. CRC Press, Inc. Boca Raton, FL, pp.397^410. Trock DH, Bollet AJ, Markoll R (1994) The e ect of pulsed electromagnetic elds in the treatment of osteoarthritis of the knee and cervical spine. Report of randomized, double blind, placebo controlled trials. J Rheumatol 21, 1903^1911. Received 8 November 2000; accepted 29 June Appendix A Cumulative pain score (modi ed from Sammarco et al. 1996) Criteria Score Observation Comfort 0 Patient asleep or calm 1 Awake, interested in surroundings 2 Mild agitation, or depressed and uninterested in surroundings 3 Moderate agitation, restless, and uncomfortable 4 Extremely agitated, thrashing Veterinary Anaesthesia and Analgesia, 2002, 29, 43^48 47

6 Appendix A continued Criteria Score Observation Movement 0 Quiet, no movement positional changes per minute positional changes per minute 3 Continuous positional changes Appearance 0 Normal 1 Mild changes: eyelids partially closed, ears flattened or carried abnormally 2 Moderate changes: eyes sunken or glazed, unthrifty appearance 3 Severe changes: eyes pale, enlarged pupils, grimacing or other abnormal facial expressions, guarding, hunched-up position, legs in abnormal position, grunting before expiration, grinding of teeth Behavior 0 Normal (unprovoked) 1 Minor changes 2 Moderately abnormal: less mobile and less alert than normal, unaware of surroundings, very restless 3 Markedly abnormal: very restless, vocalization, self-mutilation, grunting, facing back of cage Interactive 0 Normal behaviors 1 Pulls away when surgical site touched, looking at wound, mobile 2 Vocalizing when wound is touched, somewhat restless, or reluctant to move, but will move if coaxed 3 Violent reactions to stimuli, vocalizes without touching wound, snapping, growling, or hissing when approached, extremely restless, or will not move when coaxed Vocalization 0 Quiet 1 Crying, responds to calm voice and stroking 2 Intermittent crying or whimpering, no response to calm voice or stroking 3 Continuous noise that is unusual for this animal Heart rate % above pre-operative value % above pre-operative value % above pre-operative value 3 > 45% above pre-operative value RR % above pre-operative value % above pre-operative value 30 45% above pre-operative value > 45% above pre-operative value MAP % above pre-operative value % above pre-operative value % above pre-operative value 3 > 45% above pre-operative value Total 0 28 Note: In this study if total 17, institute treatment for pain immediately. RR, respiratory rate; MAP, mean arterial blood pressure. 48 Veterinary Anaesthesia and Analgesia, 2002, 29, 43^48