Formalin-Induced Differential Activation of Nucleus Cuneiformis Neurons in the Rat: An Electrophysiological Study

The midbrain neural basis underlying each phase of behavior in the formalin test has not been clarified. The present study was designed to investigate neuronal responses to formalin-induced 2-phase pain and morphine-induced antinociception in the nucleus cuneiformis (CnF) that is part of the descending pain modulatory system. Formalin-induced neuronal activities were recorded from the CnF during first and second phases of the formalin test, using an extracellular single-unit recording technique. Our results showed that: 1) the majority of neurons in the CnF displayed monophasic excitatory responses in the first or second phase after formalin injection, except a small portion of neurons which did not exhibit any responses; 2) unit activity of CnF neurons was suppressed after subcutaneous (sc) morphine administration and resumed by naloxone; 3) the increased neuronal firing induced by sc formalin could be suppressed by a single dose of sc morphine; and 4) the response patterns of many CnF neurons changed by preinjection of morphine during 2 phases of the formalin test. Our findings suggest that the diverse activity pattern in the spontaneous background of CnF neurons may have different roles in the transmission of nociceptive information induced by the peripheral noxious stimuli (eg, formalin).PerspectiveGrowing evidence shows the involvement of nucleus cuneiformis in the descending pain modulatory system. Further elucidation of the pain modulatory system could potentially lead to better understanding of pain modulation as well as development of new clinical treatments and/or strategies.