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Evaluation of Role of Septal Nuclei in Modulation of Pain in Selected Pain Models

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Evaluation of Role of Septal Nuclei in Modulation of Pain in Selected Pain Models Prakash M. Somade et al /J. Pharm. Sci. & Res. Vol. 11(6), 2019, 2233-2239 Evaluation of role of septal nuclei in modulation of pain in selected pain models Prakash M. Somade, 1 Atul R. Chopade,2 M. S. Chitale,1 Pramod A. Patil2 and Shivaji V. Brid1 1Department of Physiology, Krishna institute of medical sciences, Karad, 415539, Maharashtra, India. 2Dept. of Pharmacology, Rajarambapu college of Pharmacy, Kasegaon 415404. Maharashtra, India. Abstract The aim of the present work was to study the specific role of septal nuclei in modulation of pain. For this purpose bilateral septal lesion were done electrolytically in adult male wistar rats. The role of septal nuclei in modulation of pain was assessed by using two different pain tests such as the tail flick test and the formalin test. The histological appearance showed that electrolytic lesion site involved all the parts of septal nuclei namely medial and lateral septal nuclei and anterior and posterior groups of neurons in septal region. No attempt was made to study the role of individual parts of septal nuclei in modulation of pain. The pain threshold for thermal pain produced by radiant heat method in tail flick test was markedly low in the rats with bilateral lesions of septal nuclei, compared to the pain threshold for pain in the rats in control group. This difference in threshold was statistically significant (p<0.001). Formalin test showed typical double peaked graph when pain score was plotted against time. Thus the biphasic response described for the formalin test was confirmed. There was no statistical significant difference in the threshold for pain produced by formalin in the control and operated groups. The present work suggest that septal nuclei are involved in the processing of thermal pain sensation and its modulation, but probably not involved in the processing and modulation of chemically induced pain sensation. Key words- Septal nuclei, thermal pain, modulation. INTRODUCTION experiments. The surgical animals were housed in separate The scientific study of pain has undergone rapid polyvinyl cages under 12 hour light and dark regime [light development in recent 20 years. Neural mechanisms that on at 600 hours and off at 1800 hours] and were fed with sub serve pain though much more complex are becoming standard diet and water ad libitum. clear.1,2,3 Throughout the resurgence of attempts to A prior permission was taken from the Institutional Ethics understand pain and its mechanisms it has become Committee of Rajarambapu College of Pharmacy, increasingly apparent that pain is a multidimensional Kasegaon (RCPK) for use of rodents for the present experience consisting of sensory cognitive evaluative and research work. RCPK is registered under CPCSEA affective motivational components.1-5 Appreciation of pain [Committee for the Purpose of Control and Supervision of is considerably altered by various descending tracts Experiment on Animals]. The protocol of the present study originating in brain stem and various descending tracts was approved by the CPCSEA approved committee of originating in brainstem and various other parts of brain RCPK. above the brainstem. 1-3 It is observed that very little work 2. Chemicals and Anaesthetics is carried out as regards elucidating the role of septal Chemicals - 2.5% buffered formalin acetate was used to nuclei in modulating pain5-7. These nuclei are known to carry out formalin test. The chemicals used for perfusion play role in hyper motility, spatial mapping, reproductory of animal at the end of experimental session were formal behavior and food intake. Septal nuclei are also one of the saline and potassium ferrocyanide. The chemicals used for well established sites of self stimulation.8 Considering histological procedure were absolute alcohol and alcohol these functions and taking into account their anatomical in various concentrations of chloroform and eosin. site and connections it was planned to manipulate septal Anaesthetics- Anaesthetics used for operative procedures nuclei and study the effect on pain rating in lab bred rats. was sodium pentobarbitone (LOBA chemicals, Mumbai) In our previous study we have suggested that the septum to maintain a steady level of anaesthesia while performing may be involved in modulation of pain and electrolytic lesions in the septal nuclei. neurotransmitters like Acetylcholine, Noradrenaline and 3. Instruments opioid peptides may have an individual or collective role a) Stereotaxic instrument (Inco, Ambala, India)- to play in modulation of pain.6-7 The present study was This was used for putting electrode in the septal nuclei for meant for exploring the role of septal nuclei in modulation the purpose of sham operation and for making electrolytic of pain by using two different pain tests such as the tail lesions in the septal nuclei. It has two calibrated lateral flick test and the formalin test. bars. Calibrated aural bars are fixed at right angle to lateral bars through clamps provided. A rat head holder with MATERIALS AND METHODS longitudinal groove is present at the centre of the main 1. Animals frame. It can be moved in anterior-posterior direction. The 40 adult male Wistar rats of 150 days old and weighing head holder has a horizontal incisor bar which can be between 200gms and 220 gms were used for the moved vertically to adjust its height. A nose bar helps to 2233 Prakash M. Somade et al /J. Pharm. Sci. & Res. Vol. 11(6), 2019, 2233-2239 keep the head pressed firmly in position. The electrode is muscle were retracted after retracting the skin. The clean fitted in electrode carrier which has arrangement for bone surface with its sutural landmarks was exposed after vertical, lateral and antero-posterior movement for exact proper hemostasis. The bregma was located. After placement of electrode. adjusting the stereotaxiccoardinates for septal nuclei b) Behavioral cage - The behavioral cage used for (described below), the points were marked on the skull on observation of animals for scoring pain behavior in either sides of midline with the help of sharp stainless steel formalin test was a wood box constructed specially with pointer of the stereotaxic apparatus. The skull bone dimension 45x30x30 cms. It had transparent glass walls overlying these points was bored with the help of special from all sides and transparent glass roof. It had a sliding bone drilling screw, so as to make a hole to pass the glass door in front through which animals are introduced electrode. The stereotaxic co-ordinate was measured with in to the cage. reference to bregma. The coordinates selected for septal c) Anagesiometer- Radiant heat type, mark I nuclei were from stereotaxic atlas for rats brain and were Analgesiometer (INCO, Ambala, India) was used for tail as follows, 1] 1 mm anterior to bregma. 2] 0.5 mm on flick test. The instrument makes use of heated nichrome either side of sagital sutures line. 3] 5.5 mm deep depth wire to provide radiant heat as a pain stimulus rat’s tail. below the surface of skull bone. Unipolar electrode (gauge The description of the Analgesiometer is as follows- On 28) varnished except at the tip was placed stereotaxically top, are left hand side, there is the chrome plated water in the septal nuclei first on one side and then on the other jacket in the centre of which is nichrome wire .On the side. Another electrode was fixed to the ear of the animal. sloping panel are: 1) Pilot lamp –TO see weather current is From dry cell battery source anodal DC current adjusted flowing through the nichrome wire. 2) On –off switch. 3) through multimiter to 1.5 milliamperes was passed for 20 Ampere meter – To adjust and keep constant amount of seconds. This was done on either side to make the anodal current flowing through the nichrome wire. lesions bilaterally in the septal nucei. In case of sham Operation of the instrument- One end of water jacket is operated group (sham group) the whole procedure attached to a water tap by suitable rubber tubing. To remained the same except that no current was passed another end of water jacket is attached another rubber through the electrode. After the procedure was over, tubing to allow the water to run waste. During experiments electrode was taken out, the skin was sutured and the site free circulation of water is maintained through the water was cleaned with spririt. Nebasulf powder was applied. jacket to provide a constant ambient temperature around Injection benezathine penicillin 10,000 I U was given the stimulus area. Instrument is connected to 250 volt A.C intramuscularly and animal was transferred to its cage. supply. When switch on, the pilot lamps light up. The The animals were observed for 7 days post-operatively knob on the ampere meter is adjusted so that desired fixed when the aggressive behavior or such other affective amount of current flows through the nichrome wire. responses disappeared. Septally lesioned 20 animals were Before doing the test procedure, it is seen that every time divided in to two groups consisting of 10 animals each. same amount of current flows through the nichrome wire. One septally lesioned group and one sham operated group Experiments are generally carried out with current of the and sham operated group underwent tail flick test. amplitude between 3 and 4 amperes flowing through the B] The formalin test 10,11,12 nichrome wire. During the test, the rat is placed in the rat The details regarding formalin test are given below: The carrier with its tail protruding through the specially cut slit formalin testing was performed as described for rats. Each in the shutter of the carrier. The rat carrier is held with the rat was habituated to behavioral cage for 1 hour in a day of right hand on the top of the instrument.
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