The possible mechanisms of analgesia produced by microinjection of morphine into the lateral habenula in the acute model of trigeminal pain in rats

Abstract

This study aimed to assess the effect of intra-habenular injection of morphine on acute trigeminal pain in rats. Also here, we examined the involvement of raphe nucleus opioid and 5HT3 receptors on the antinociceptive activity of intra habenular morphine to explore the possibility of existence of descending antinociceptive relay between the habenula and raphe nucleus. The numbers of eye wiping response elicited by applying a drop (40 μL) of NaCl (5 M) solution on the corneal surface were taken as an index of acute trigeminal nociception. Intra habenular microinjection of morphine at a dose of 2 μg was without effect, whereas at doses of 5 and 8 μg significantly produced antinociception. Microinjection of naltrexone (4 μg) and ondansetron (1 μg) into the dorsal raphe nucleus prior to intra-habenular saline did not produce any significant effect on corneal pain perception. Pretreatment of the raphe nucleus with ondansetron but not naltrexone prevented intra habenular morphine (8 μg) induced antinociception. Also, intra habenular injection of lidocaine (2%, 0.5 μL reduced corneal pain response. Moreover, intra-habenular microinjection of L-glutamic acid (1 and 2 μg/site) did not produce any analgesic activity in this model of pain. In conclusion, the present results suggest that the activation of the habenular μ opioid receptor by microinjection of morphine or inhibition of habenular neurons by microinjection of lidocaine produced an analgesic effect in the acute trigeminal model of pain in rats. The analgesic effect of intra habenular morphine was blocked by intra-dorsal raphe injection of serotonin 5-HT3 antagonist.

Downregulation of M-channels in lateral habenula mediates hyperalgesia during alcohol withdrawal in rats

“…Compared with traditional excitotoxic lesions and pharmacologic interventions, chemogenetic approaches have the advantage of greater ability to transiently regulate a specific population of neurons 42 . Our observation that silencing LHb excitatory neurons reduced thermal hypersensitivity is consistent with previous pharmacologic intervention studies 9,21 .…”

“…LHb disturbances have been implicated in the pathogenic interrelation between pain and psychiatric disorders 18–20 . Indeed, pharmacological inhibition of activity of LHb neurons is analgesic 9,21 . A study indicates that reduction of LHb M-channels, a voltage-gated potassium channel contributes to increased excitability of LHb neurons of ethanol-withdrawn rats 22 .…”

Mechanisms of Peripheral and Central Pain Sensitization: Focus on Ocular Pain

“…A recent study has described the involvement of habenular complex in the descending control of corneal pain: nociception induced by corneal application of saline can be inhibited by administration to habenula of morphine or lidocaine. Pre-treatment of the NRM with the 5-HT3 antagonist ondansetron prevented the effect of morphine on habenula, confirming the modulatory role played by this area on serotoninergic pathways (Khalilzadeh and Saiah, 2017).…”

Alterations in pain processing circuitries in episodic migraine

“…The NAc is associated with the reward system and survival behaviors that reduce the possibility of injury or damage signaled by pain are negatively reinforced [ 38 ]. In experimental animal studies, analgesic responses can be evoked by injections of morphine into either the PAG or NAc [ 39 , 40 ] and we have previously shown in humans that the NAc is involved in conditional pain modulation (CPM) analgesia [ 41 ]. Although the NAc receives input from the PFC and projects indirectly to the PAG [ 42 ], we found no differences in either whole scan or pain-related changes in connectivity between the NAc and other brain regions.…”