Effect of Rohypnol on Pain Threshold and Acoustic Startle Reflex in Wistar Rats

Victor Opuada Hart *

Department of Human Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Port Harcourt, P.M.B. 5323, Choba, Port Harcourt, Nigeria.

Austin Azubuike Ajah

Department of Human Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, University of Port Harcourt, P.M.B. 5323, Choba, Port Harcourt, Nigeria.

*Author to whom correspondence should be addressed.


Abstract

Some physical and psychological factors resulting in heterogeneous pain have been implicated to either increase or decrease pain thresholds. Rohypnol which produces both sedative and muscle relaxant effects, is a choice drug for abusers and addicts. This study investigated the effect of Rohypnol on pain threshold and acoustic startle reflex in Wistar rats.

Twenty-five (25) female Wistar rats (160–180g) were randomly grouped into five groups (A-E) of five rats each, sequel to their acclimatization under standard ethical conditions. Rats in group A served as the control and received 0.5mL distilled water once daily. Rats in group B received 2mg/kg Diclophenac Sodium (DIC) once daily; while rats in groups C, D and E received 3mg/kg Rohypnol, once, twice and thrice daily, respectively. Treatment to rats in all groups lasted eight days. All rats received standard feed and water ad libitum throughout the study. Pain threshold was assessed using analgesy-meter and tail-clip tests; while acoustic startle reflex (ASR) response time was assessed using an acoustic bell.

The results revealed a significant increase in pain threshold in groups B and E on days 2, 4, 6 and 8 (6.40±0.48 and 8.32±0.20; 6.93±0.32 and 7.00±0.20; 6.95±0.31 and 8.93±1.30; 7.05±0.29 and 9.66±0.71 seconds, respectively) compared to the control (4.7±0.23; 5.26±0.44; 5.01±0.38; 5.06±0.30 seconds). Pain threshold in group D significantly increased on days 6 and 8 (7.00±0.12 and 7.03±0.34 seconds, respectively). An increase in ASR response time was observed in the treated rat groups compared to the control, except on day 4 where the response time in group D was significantly increased compared to the control (2.47±0.08 vs. 1.80±0.13 seconds).

This finding highlights the analgesic effect of Rohypnol in reducing pain hypersensitivity, which may be attributed to the muscle tone depression, lack of muscle alertness, and the increase in ASR response associated with the drug.

Keywords: Rohypnol, pain threshold, pain hypersensitivity, acoustic startle reflex, diclophenac


How to Cite

Hart , V. O., & Ajah , A. A. (2023). Effect of Rohypnol on Pain Threshold and Acoustic Startle Reflex in Wistar Rats. South Asian Research Journal of Natural Products, 6(3), 134–143. Retrieved from https://www.journalsarjnp.com/index.php/SARJNP/article/view/119

Downloads

Download data is not yet available.

References

IASP. IASP pain terminology. IASP press. Archived from the threshold of pain. In Wikipedia; 2022.

Available:https://en.wikipedia.org/wiki/Threshold_of_pain

Kouyanou K, Pither CE, Wessely S. Latrogenic factors and chronic pain. Psychosom Med. 1997;59(6):597–604.

Strong J. Pain: A text book for therapists, Japanese edition. Nagoya: The University of Nagoya press; 2002.

Raj PP, Chado HN, Angst M, Heavner J, Dotson R, Brandstater ME, Johnson B, Parris W, Finch P, Shahani B, Dhand U, Mekhail N, Daoud E, Hendler N, Somerville J, Wallace M, Panchal S, Glusman S, Jay GW, Palliyath S, Longton W, Irving G. Painless electrodiagnostic current perception threshold and pain tolerance threshold values in CRPS subjects and healthy controls: a multicenter study. Pain Pract. 2001;1:53–60.

Wallin M, Liedberg G, Börsbo B, Gerdle B. Thermal detection and pain thresholds but not pressure pain thresholds are correlated with psychological factors in women with chronic whiplash-associated pain. Clin. J. Pain. 2012;28:211–21.

Bär KJ, Brehm S, Boettger MK, Boettger S, Wagner G, Sauer H. Pain perception in major depression depends on pain modality. Pain. 2005;117:97–103.

Jiang ZC, Qi WJ, Wang JY, Luo F. Chronic administration of 5-HT1A receptor agonist relieves depression and depression-induced hypoalgesia. Scientific World Journal. 2014;2014:405736.

Dickens C, McGowan L, Dale S. Impact of depression on experimental pain perception: a systematic review of the literature with meta-analysis. Psychosom Med. 2003;65:369–75.

Sheng J, Liu S, Wang Y, Cui R, Zhang X. The Link between Depression and Chronic Pain: Neural mechanisms in the brain. Neural Plast. 2017;2017:9724371.

Crosbie TW, Packman W, Packman S. Psychological aspects of patients with Fabry disease. J Inherit Metab Dis. 2009;32:745–53. DOI: 10.1007/s10545-009-1254-1.

Braff DL, Geyer MA, Swerdlow NR. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharm (Berlin). 2001;156:234–258.

Geyer MA, Braff DL. Startle habituation and sensorimotor gating in schizophrenia and related animal models. Schizophr Bull. 1987;13:643–668.

Davis M, Falls WA, Campeau S, Kim M. Fear-potentiated startle: a neural and pharmacological analysis. Behav Brain Res. 1993;58:175–198.

Grillon C. Startle reactivity and anxiety disorders: aversive conditioning, context, and neurobiology. Biol Psychiatry. 2002;52:958–975.

Grillon C, Morgan CA, Southwick SM, Davis M, and Charney S. Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder. Psychiatry Res. 1996;64:169–178.

Meincke U, Light GA, Geyer MA, Braff DL, and Gouzoulis-Mayfrank E. Sensitization and habituation of the acoustic startle reflex in patients with schizophrenia. Psychiatry Res. 2004;126:51–61.

Ludewig S, Geyer MA, Ramseier M, Vollenweider FX, Rechsteiner E, Cattapan-Ludewig K. Information-processing deficits and cognitive dysfunction in panic disorder. J Psychiatry Neurosci. 2005;30:37–43.

Gallo FJ, Klein-Tasman BP, Gaffrey MS, Curran P. Expecting the worst: observations of reactivity to sound in young children with Williams syndrome. Res Dev Disabil. 2008;29:567–581.

Madsen GF, Bilenberg N, Cantio C, Oranje B. Increased prepulse inhibition and sensitization of the startle reflex in autistic children. Autism Res. 2014;7:94–103.

Szabo I. Analysis of the muscular action potentials accompanying the acoustic startle reaction. Acta Physiol Hung. 1964;27: 167-178.

Graham FK. Distinguishing among orienting, defense, and startle reflexes. In: The orienting reflex in humans (Eds. H.D. Kimmel, E.H. van Olst and J.F.Orlebeke). Lawrence Erlbaum Associates Publishers, Hillsdale, New Jersey. 1979; 137-167.

Hoffman HS, Ison JR. Reflex modification in the domain of startle: I. Some empirical findings and their implication for how the nervous system processes sensory input. Psychol Rev. 1980;87:175-189.

Ison JR and Russo JM. Enhancement and depression of tactile and acoustic startle reflex with variation in background noise level. Psychobiology. 1990;18: 96-100.

Seaman RL, Beblo DA, Raslear TG. Modification of acoustic and tactile startle by single microvawe pulses. Physiol Behav. 1994;55:587-595.

Stitt CL, Hoffman HS, Marsh RR, Schwartz GM. Modification of the pigeon’s visual startle reaction by sensory environment. J Comp Physiol Psychol. 1976;90:601-619.

Woodworth CH, Johnson AK. Isolation, tactile startle and resting blood pressure in Long-Evans rats. Physiol. Behav. 1988;43: 609-616.

Davis M. Animals models of anxiety based on classical conditionig: The conditioned emotional response (CER) and the fear-potentiated startle effect. Pharmacol Ther. 1990;47:147-165.

Koch M. The neurobiology of startle. Prog Neurobiol. 1999;59:107-128.

Geller A. Neurological effects. In: Graham, A.W., and Wilford, B.B., eds. Principles of Addiction Medicine. 2d ed. Chevy Chase, MD: American Society of Addiction Medicine, 1998;775–792.

File S. The history of benzodiazepam dependence: a review of animal studies. Neuroscience and Biobehavioral Review. 1990;14:135-146.

Fish EW, Mckenzie-Quirk SD, Bannai M, and Miczek KA. 5-HT [1B] receptor inhibition of alcohol-heightened aggression in mice: comparison to drinking and running. Psychopharmacology [Berl]. 2008;197:145-156.

Mattila MAK, Larni HM. Flunitrazepa m : a review of itspharmacological properties and therapeutic use. Drugs. 1980;20:353-374.

Kales A, Scharf MB, Kales JD, Soldatos CR. Rebound Insomnia. A potential hazard following withdrawal of certain benzodiazepines. Journal of the American Medical Association. 1979;241(16): 1692–5.

Druid H, Holmgren P, Ahlner J. Flunitrazepam: an evaluation of use, abuse and toxicity. Forensic Sci Int. 2001;122(2–3):136–41.

Hesse ML, Venkatakrishnan K, Von Moltke LL, Shader RI, and Greenblatt DJ. CYP3A4 is the major CYP isoform mediating the in vitro hydroxylation and demethylation of flunitrazepam. Drug Metabolism & Disposition. 2001;29(2):133–40.

Miller RL. Drugs of abuse: a reference guide to their history and use. Westport, Conn.: Greenwood Press. 2002;168.

FarrÈ M, Teran MT and CamÌ J. A comparison of the acutebehavioral effects of flunitrazepam and triazolam in healthy vol-unteers. Psychopharmacology. 1996; 125:1-12.

FarrÈ M and CamÌ J. Pharmacokinetic considerations in abuseliability evaluation. Br J Addict. 1991;86:1601-1606.

Arendt RM, Greenblatt DJ, deJong RH, Bonin JD, Abernathy DR,Ehrenberg BL, Giles HG, Sellers EM, Shader IR. In vitrocorrelates of benzodiazepine cerebrospinal fluid uptake, phar -macodynamic action and peripheral distribution. J Pharmacol Exp Ther. 1993;227:98-106.

Albus U. Guide for the care and use of laboratory animals (8th edn). SAGE Publications Sage UK: London, England; 2012.

Benjamin B. Overview of laboratory animal lifestyle, care, and management: a case study of albino rats. Journal of Applied Sciences and Environmental Management. 2019;23(8):1431-5.

Bowery NG. GABA receptor pharmacology. In: Sieghart W. ed. Handbook of Experimental Pharmacology. Berlin Springer. 2002;154:283-33.

Hindmarch I, ElSohly M, Gambles J, Salamone S. Pharmacological effects of the benzodiazepine receptor agonist, flunitrazepam, on cognitive and psychomotor function. Psychopharmacology (Berl). 1989;98(1): 65-73.

Ong CK, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis. Anesth Analg. 2005;100(3): 757-773.

Landis C, Hunt W. The Startle Pattern. Farrar & Rinehart; New York, NY, USA; 1939.

Swerdlow NR, Geyer MA, Vale WW, Koob GF. Corticotropin-releasing factor potentiates acoustic startle in rats: blockade by chlordiazepoxide. Psychopharmacology (Berl). 2000;148(3): 267-274.