Document Type : Original Article

Authors

1 PhD Candidate, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

Abstract

The aim of the present study was to investigate the effects of intra-ventrolateral periaqueductal gray (vlPAG) microinjection of histamine and thioperamide (a histamine H3 receptor antagonist/inverse agonist) on neuropathic pain. To explore the possible mechanism, naloxone was microinjected alone or in combination with histamine and thioperamide. Neuropathic pain was induced by the left sciatic nerve chronic constriction injury. Both the right and left sides of vlPAG of the brain were surgically cannulated. Cold allodynia and mechanical hyperalgesia were recorded by acetone evaporation and von Frey filament tests. Areas under curve of allodynia and hyperalgesia were calculated. Histamine (0.50 and 2.00 µg per site), thioperamide (4.00 µg per site) and thioperamide (4.00 µg per site) before histamine (2.00 µg per site) suppressed cold allodynia and mechanical hyperalgesia after microinjection into the vlPAG. Microinjection of naloxone (0.25 and 1.00 µg per site) into the vlPAG had no effect on cold allodynia and mechanical hyperalgesia. The anti-allodynic and anti-hyperalgesic effects induced by microinjection of histamine (2.00 µg per site) and thioperamide (4.00 µg per site) into the vlPAG were inhibited by prior microinjection of naloxone (1.00 µg per site) into the same site. The above-mentioned agents did not alter locomotor activity. Based on our present results, it was concluded that exogenous (by histamine microinjection) and endogenous (by thioperamide microinjection) histamine of the vlPAG might contribute to the descending pain control mechanisms through a naloxone-sensitive mechanism.

Keywords

  1.  Zilliox LA. Neuropathic pain. Continuum (Minneap Minn) 2017; 23(2): 512-532.
  2. Meacham K, Shepherd A, Mohapatra DP, et al. Neuropathic pain: central peripheralmechanisms. Curr Pain Headache Rep 2017; 21(6): 28. doi: 10.1007/s11916-017-0629-5.
  3. Menant O, Andersson F, Zelena D, et al. The benefits of magnetic resonance imaging methods to extend the knowledge of the anatomical organization of the periaqueductal gray in mammals. J Chem Neuroanat 2016; 77: 110-120.
  4. De Felice M, Ossipov MH. Cortical and subcortical modulation of pain. Pain Manag 2016; 6(2): 111-120.
  5. George DT, Ameli R, Koob GF. Periaqueductal gray sheds light on dark areas of psychopathology. Trends Neurosci 2019; 42(5): 349-360.
  6. Brown RE, Stevens DR, Haas HL. The physiology of brain histamine. Prog Neurobiol 2001; 63(6): 637-672.
  7. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev 2008; 88(3): 1183-1241.
  8. Obara I, Telezhkin V, Alrashdi I, et al. Histamine, histamine receptors, and neuropathic pain relief. Br J Pharmacol 2020; 177(3): 580-599.
  9. Hamzeh-Gooshchi N, Tamaddonfard E, Farshid AA. Effects of microinjection of histamine into the anterior cingulate cortex on pain-related behaviors induced by formalin in rats. Pharmacol Rep 2015; 67(3): 593-599.
  10. Erfanparast A, Tamaddonfard E, Taati M, et al. Role of the thalamic submedius nucleus histamine H1 and H2 and opioid receptors in modulation of formalin-induced orofacial pain in rats. Naunyn Schmiedebergs Arch Pharmacol 2015; 388(10): 1089-1096.
  11. Khalilzadeh E, Tamaddonfard E, Farshid AA, et al. Microinjection of histamine into the dentate gyrus produces antinociception in the formalin test in rats. Pharmacol Biochem Behav 2010; 97(2):325-332.
  12. Salimi S, Tamaddonfard E. Microinjection of histamine and its H3 receptor agonist and antagonist into the agranular insular cortex influence sensory and affective components of neuropathic pain in rats. Eur J Pharmacol 2019; 857: 172450. doi: 10.1016/j.ejphar. 2019.172450.
  13. Khalilzadeh E, Azarpey F, Hazrati R, et al. Evaluation of different classes of histamine H1 and H2 receptor antagonist effects on neuropathic nociceptive behavior following tibial nerve transection in rats. Eur J Pharmacol 2018; 834: 221-229.
  14. Fischer IW, Hansen TM, Lelic D, et al. Objective methods for the assessment of the spinal and supra-spinal effects of opioids. Scand J Pain 2017; 14: 15-24.
  15. Bodnar RJ, Endogenous opiates and behavior: 2016. Peptides 2018; 101: 167-212.
  16. Pillot C, Heron A, Cochois V, et al. A detailed mapping of the histamine H(3) receptor and its gene transcripts in rat brain. Neuroscience 2002; 114(1): 173-193.
  17. Eippert F, Bingel U, Schoell ED, et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 2009; 63(4): 533-543.
  18. Bennett GJ, Xie Y-K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33(1): 87-107.
  19. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 4th Massachusetts, USA: Academic Press 1998: 50-52.
  20. Deuis JR, Dvorakova LS, Vetter I. Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci 2017; 10: 284. doi: 10.3389/fnmol. 2017.00284.
  21. Espinosa-Juárez JV, Jaramillo-Morales OA, Navarrete-Vázquez G, et al. N-(2-morpholin-4-yl-ethyl)-2-(1naphthyloxy) acetamide inhibits the chronic constriction injury-generated hyperalgesia via the antagonism of sigma-1 receptors. Eur J Pharmacol 2017; 812: 1-8. doi: 10.1016/j.ejphar.2017.06.026.
  22. Cardoso FC, Sears W, LeBlanc SJ, et al. Technical note: comparison of 3 methods for analyzing areas under the curve for glucose and nonesterified fatty acids concentrations following epinephrine challenge in dairy cows. J Dairy Sci 2011; 94(12): 6111-6115.
  23. Wang GQ, Sun WP, Zhu YJ, et al. H(1) and H(2) receptors in the locus ceruleus are involved in the intracerebro-ventricular histamine-induced carotid sinus baroreceptor reflex resetting in rats. Neurosci Bull 2006; 22(4): 209-215.
  24. Niaz N, Guvenc G, Altinbas B, et al. Intra-cerebro-ventricular injection of histamine induces the hypothalamic-pituitary-gonadal axis activation in male rats. Brain Res 2018; 1699: 150-157.
  25. Thoburn KK, Hough LB, Nalwalk JW, et al. Histamine-induced modulation of nociceptive responses. Pain 1994; 58(1): 29-37.
  26. Barceló AC, Filippini B, Pazo JH. The striatum and pain modulation. Cell Mol Neurobiol 2012; 32(1): 1-12. doi: 10.1007/s10571-011-9737-7.
  27. Huang L, Adachi N, Nagaro T, et al. Histaminergic involvement in neuropathic pain produced by partial ligation of the sciatic nerve in rats. Reg Anesth Pain Med 2007; 32(2): 124-129.
  28. Lu C, Yang T, Zhao H, et al. Insular cortex is critical for the perception, modulation, and chronification of pain. Neurosci Bull 2016; 32(2): 191-201.
  29. Wei H, Jin CY, Viisanen H, et al. Histamine in the locus coeruleus promotes descending noradrenergic inhibition of neuropathic hypersensitivity. Pharmacol Res 2014; 90: 58-66.
  30. Xiao X, Zhang YQ. A new perspective on the anterior cingulate cortex and affective pain. Neurosci Biobehav Rev 2018; 90: 200-211.
  31. Trescot AM, Datta S, Lee M, et al. Opioid pharmacology. Pain Physician 2008; 11(2 Suppl): S133-S153.
  32. Yoshida K, Nonaka T, Nakamura S, et al. Microinjection of 26RFa, an endogenous ligand for the glutamine RF-amide peptide receptor (QRFP receptor), into the rostral ventromedial medulla (RVM), locus coelureus (LC), and periaqueductal grey (PAG) produces an analgesic effect in rats. Peptides 2019; 115: 1-7. doi: 10.1016/j.peptides.2019.02.003.
  33. Sohn JH, Lee BH, Park SH, et al. Microinjection of opiates into the periaqueductal gray matter attenuates neuropathic pain symptoms in rats. Neuroreport 2000; 11(7): 1413-1416.
  34. Wei H, Panula P, Pertovaara A. A differential modulation of allodynia, hyperalgesia and nociception by neuropeptide FF in the periaqueductal gray of neuropathic rats: interactions with morphine and naloxone. Neuroscience 1998; 86(1): 311-319.