Mu-opioidergic modulation differs in deep and superficial wide-dynamic range dorsal horn neurons in mice

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 (0.5 mM, 30 μl) and naloxone (1 mM, 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.