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Updated: May 10, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Mu-opioidergic modulation differs in deep and superficial wide-dynamic range dorsal horn neurons in mice
Qian Xu1, Wei-Yan Li, Yun Guan
1Department of Clinical Pharmacology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China.
Abstract:
The spinal cord dorsal horn is an important action site for morphine analgesia. Wide-dynamic range (WDR) neurons in the dorsal horn are essential to spinal pain transmission and show increased excitability after repetitive noxious drive (windup). In light of differences in mu-opioid receptor distribution and neurophysiological properties of WDR neurons between deep and superficial dorsal horn, we recorded extracellular single-unit activity of WDR neurons from deep (350-700 μm) and superficial (<350 μm) dorsal horn in C57BL/6 mice and compared their responses to spinal superfusion of morphine (0.5mM, 30 μl) and naloxone (1mM, 30 μl). The windup level to repetitive electrical stimulation of 1.0 Hz (16 pulses, suprathreshold for C-fiber activation, 2.0 ms) was significantly decreased by morphine in deep (n=8), but not superficial (n=11), WDR neurons. However, the steady C-component response to graded intra-cutaneous electrical stimuli (0.01-5.0 mA, 2 ms) was significantly depressed by morphine only in superficial neurons. In separate experiments, spinal administration of naloxone facilitated the development of windup to 0.2 Hz stimulation in deep (n=10), but not superficial (n=8), WDR neurons. Accordingly, morphine and naloxone modulation of neuronal activity may be related to a specific effect on neuronal sensitization/plasticity in deep WDR neurons, whereas morphine inhibition may depress acute noxious inputs to superficial WDR neurons. Our study suggests that mu-opioidergic modulation may be different in deep and superficial WDR neurons.
Insights
Morphine reduces pain signals in deep dorsal horn neurons but not superficial ones. Naloxone, however, enhances pain signals in deep neurons, suggesting distinct mu-opioid effects in different spinal cord layers.
Area of Science:
- Neuroscience
- Pain Research
- Pharmacology
Background:
- The spinal cord dorsal horn is a key site for morphine's pain-relieving effects.
- Wide-dynamic range (WDR) neurons in the dorsal horn transmit pain signals and exhibit windup (increased excitability) after repetitive noxious stimuli.
- Differences in mu-opioid receptor distribution and WDR neuron properties exist between superficial and deep dorsal horn layers.
Purpose of the Study:
- To investigate the differential effects of morphine and naloxone on WDR neurons in the superficial and deep dorsal horn.
- To explore the distinct mechanisms of mu-opioidergic modulation in different spinal cord laminae.
Main Methods:
- Extracellular single-unit activity of WDR neurons was recorded in C57BL/6 mice.
- Responses were compared between deep (350-700 μm) and superficial (<350 μm) dorsal horn neurons.
- Spinal superfusion with morphine (0.5mM) and naloxone (1mM) was performed, along with electrical stimulation protocols to induce windup and assess C-component responses.
Main Results:
- Morphine significantly decreased windup in deep WDR neurons but not superficial ones.
- Morphine significantly depressed the steady C-component response in superficial WDR neurons only.
- Spinal naloxone facilitated windup in deep WDR neurons but not superficial ones.
Conclusions:
- Mu-opioidergic modulation differs between deep and superficial WDR neurons.
- Morphine's effects on neuronal sensitization/plasticity appear specific to deep WDR neurons.
- Morphine may inhibit acute noxious inputs to superficial WDR neurons, while affecting plasticity in deep WDR neurons.
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