Neuroscience Letters 451 (2009) 165–169 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Effects of electrolytic lesion of dorsolateral periaqueductal gray on analgesic response of morphine microinjected into the nucleus cuneiformis in rat Abbas Haghparast ∗ , Leila Ahmad-Molaei Neuroscience Research Center, Shahid Beheshti University, M.C., P.O. Box 19615-1178, Tehran, Iran article info Article history: Received 1 December 2008 Received in revised form 25 December 2008 Accepted 29 December 2008 Keywords: Nucleus cuneiformis Dorsolateral periaqueductal gray Morphine antinociception Electrolytic lesion Tail-flick test Formalin test abstract The periaqueductal gray (PAG) and nucleus cuneiformis (CnF), like the rostral ventromedial medulla, have functional roles in descending pain-inhibitory pathway related to morphine antinociception. There is not any evidence concerning the role of different regions of the PAG on antinociceptive effect of morphine administered into the CnF in pain modulatory system. In the present study, we investigate whether electrolytic lesion of dorsolateral periaqueductal gray (dl-PAG) influence the analgesic effect of morphine microinjected into the CnF. 71 adult male Wistar rats weighting 230–280 g cannulated bilaterally into the CnF, concurrently lesion of dl-PAG was done. The tail-flick and formalin tests were performed to measure pain and antinociceptive effect of morphine microinjected into the CnF (2.5 g/0.3 l saline per side). The tail-flick latency was measured at 15, 30, 45, 60 and 75min following morphine microinjection. In formalin test, pain behavior was recorded for 60 min in early (0–5 min) and late (15–60 min) phases after formalin injection. Each rat was given a subcutaneous 50-l injection of formalin 2.5% into plantar surface of hind paw following morphine administration. The results showed that dl-PAG lesion attenuated the effect of morphine microinjected into the CnF both in tail-flick and formalin tests while dl-PAG lesion solely did not alter basal pain behavior as compared to control group. In conclusion, our results suggest the existence of a direct or indirect projection from CnF to the dl-PAG at least at the level of the morphine antinociception in pain modulation. © 2009 Elsevier Ireland Ltd. All rights reserved. The periaqueductal gray (PAG) region of the midbrain of vertebrates including rodents and humans is recognized as one of several sites involved in the modulation of nociceptive sensory input through descending controls to the level of spinal cord [2,25]. Beitz [5] showed that PAG receives some mesencephalic inputs from the nucleus cuneiformis (CnF). Projections to caudal CnF were also observed from all subdivisions of the PAG, the deep layers of supe- rior colliculus as well as the caudal levels of CnF [29]. Retrograde tracer studies in animals have shown these two nuclei to be con- nected with each other [6,30]. Some anatomical and physiological studies have demonstrated that a major source of afferents to nucleus raphe magnus (NRM) has critical role in morphine antinoci- ception in pain modulatory system, arise from a continuous band of cells located within the PAG [7]. Human imaging studies have shown that the PAG [7] and CnF [30] are activated during vis- ceral and somatic pain [11]. The cuneiformis nucleus, a reticular nucleus of the midbrain, located just ventrolateral to the periaque- ductal gray, plays a key role in the development of experimental secondary hyperalgesia via possible facilitatory pro-nociceptive ∗ Corresponding author. Tel.: +98 21 2243 1624; fax: +98 21 2243 1624. E-mail address: haghparast@yahoo.com (A. Haghparast). mechanisms and these two nuclei involved in a network mediat- ing anti- and pro-nociception, as largely shown from animal data [12,24,28]. Our previous studies have shown that morphine when microin- jected into the CnF produced powerful analgesia in tail-flick [13–15] as a model of acute pain. In a pilot study which was carried out in this laboratory, it was revealed that spontaneous activity of CnF neurons significantly increased following formalin test as a model of chronic pain. In addition, our previous study, it was indicated that bilateral electrolytic lesion of NRM [14] but not ven- trolateral periaqueductal gray diminished analgesic response of morphine microinjected into the CnF (unpublished data). Regard- ing to the above mentioned studies that imply there are functional link between PAG and CnF, it is the aim of this study to investi- gate the role of dorsolateral periaqueductal gray as another part of PAG in antinociceptive response of morphine microinjected into the nucleus cuneiformis in rat. The experiments were performed on 71 Wistar rats (Pasteur Institute, Iran) weighing 230–280 g. Animals were kept under stan- dard laboratory conditions, with tap water and regular rat chow ad libitum. They were individually housed in a temperature and humidity-controlled vivarium on 12-h light/dark cycle. All experi- ments executed with the Guide for the Care and Use of Laboratory 0304-3940/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2008.12.058