Cornea-responsive medullary dorsal horn neurons: Modulation by local opioids and projections to thalamus and brain stem

Previously, it was determined that microinjection of morphine into the caud al portion of subnucleus caudalis mimicked the facilitatory effects of intr avenous morphine on cornea-responsive neurons recorded at the subnucleus in terpolaris/caudalis (Vi/Vc) transition region. The aim of the present study was to determine the opioid receptor subtype(s) that mediate modulation of corneal units and to determine whether opioid drugs affected unique classe s of units. Pulses of CO2 gas applied to the cornea were used to excite neu rons at the Vi/Vc ("rostral" neurons) and the caudalis/upper cervical spina l cord transition region (Vc/C1, "caudal" neurons) in barbiturate-anestheti zed male rats. Microinjection of morphine sulfate (2.9-4.8 nmol) or the sel ective mu receptor agonist D-Ala, N-Me-Phe, Gly-ol-enkephalin (DAMGO; 1.8-1 5.0 pmol) into the caudal transition region enhanced the response in 7 of 2 7 (26%) rostral units to CO2 pulses and depressed that of 10 units (37%). M icroinjection of a selective delta {[D-Pen(2,5)] (DPDPE); 24-30 pmol} or ka ppa receptor agonist (U50488; 1.8-30.0 pmol) into the caudal transition reg ion did not affect the CO2-evoked responses of rostral units. Caudal units were inhibited by local DAMGO or DPDPE but were not affected by U50,488H. T he effects of DAMGO and DPDPE were reversed by naloxone (0.2 mg/kg iv). Int ravenous morphine altered the CO2-evoked activity in a direction opposite t o that of local DAMGO in 3 of 15 units, in the same direction as local DAMG O but with greater magnitude in 4 units, and in the same direction with equ al magnitude as local DAMGO in 8 units. CO2-responsive rostral and caudal u nits projected to either the thalamic posterior nucleus/zona incerta region (PO/ZI) or the superior salivatory/facial nucleus region (SSN/VII). Howeve r, rostral units not responsive to CO2 pulses projected only to SSN/VII and caudal units not responsive to CO2 projected only to PO/ZI. It was conclud ed that the circuitry for opioid analgesia in corneal pain involves multipl e sites of action: inhibition of neurons at the caudal transition region, b y intersubnuclear connections to modulate rostral units, and by supraspinal sites. Local administration of opioid agonists modulated all classes of co rneal units. Corneal stimulus modality was predictive of efferent projectio n status for rostral and caudal units to sensory thalamus and reflex areas of the brain stem.