The effects of morphine on basal neuronal activities in the lateral and medial pain pathways

Abstract

Numerous studies indicate that morphine suppresses pain-evoked activities in both spinal and supraspinal regions. However, little is known about the effect of morphine on the basal brain activity in the absence of pain. The present study was designed to assess the effects of single-dose morphine on the spontaneous discharge of many simultaneously recorded single units, as well as their functional connections, in the lateral pain pathway, including the primary somatosensory cortex (SI) and ventral posterolateral thalamus (VPL), and medial pain pathway, including the anterior cingulate cortex (ACC) and medial dorsal thalamus (MD), in awake rats. Morphine (5mg/kg) was administered intraperitoneally before the recording. Naloxone plus morphine and normal saline injections were performed respectively as controls. The results showed that morphine administration produced significant changes in the spontaneous neuronal activity in more than one third of the total recorded neurons, with primary activation in the lateral pathway while both inhibition and activation in the medial pathway. Naloxone pretreatment completely blocked the effects induced by morphine. In addition, the correlated activities between and within both pain pathways was exclusively suppressed after morphine injection. These results suggest that morphine may play different roles in modulating neural activity in normal vs. pain states. Taken together, this is the first study investigating the morphine modulation of spontaneous neuronal activity within parallel pain pathways. It can be helpful for revealing neuronal population coding for the morphine action in the absence of pain, and shed light on the supraspinal mechanisms for preemptive analgesia.

Fig. 1

The changes of spontaneous neuronal activity after administration of morphine, normal saline (NS), or naloxone plus morphine (NAL+MOR). (A) Cluster plot depicting different neuronal response patterns (C1-C4) following morphine injection. (B) & (C) Cluster plot showing the neuronal response after NS and NAL+MOR treatments. (D) Summed population data (top let) as well as time-histogram examples of individual neurons for each cluster and during different treatments. The firing rates were transferred into z-scores, as indicated by the colorbar (light yellow for highest and light blue for lowest). Clusters with z-scores > 2 were accepted as significantly excited and < -2 as significantly inhibited.

Fig. 2

Temporal response patterns of medial and lateral pathway neurons following morphine administration. (A) Neurons in the medial pathway (ACC and MD) showed both excitatory and inhibitory responses to morphine administration. In contrast, the neuronal response in the lateral pathway (SI and VPL) was predominantly excitatory. (B) Percentage of neurons exhibiting excitatory or inhibitory responses to morphine administration over time. Morphine was injected at time zero.

Fig. 3

Cross-correlogram plots of eight simultaneously recorded neurons from the ACC and MD thalamus (5 ACC and 3 MD) during morphine (left) and NS (right) sessions. Five significant correlations were found during NS session (indicated by asterisks). Morphine administration eliminated the correlated activity seen in NS session.

Fig. 4

Histological verification (A) as well as schematic illustration (B) of the recording electrode tips. Arrows indicate the recording sites (blue dots) in each area.