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One micrograms of tetracaine in the rat periaqueductal gray (PAG) produced a decline in baseline tail-flick latencies (hyperalgesia) from about 5 to 3.5 s over the course of 9 min, after which the latencies increased to about 4.5 s. One micrograms of Met-enkephalin in PGC caused an expected increase in latencies (analgesia) from about 4.25 to 6.2 s in 9 min, with recovery to 4.7 s after 15 min post-injection. Giving the preceding 2 nanoinjections simultaneously led to an essentially total block of the PGC analgesia. A control injection in PAG simultaneous with a Met-enkephalin injection in PGC did not block the latter's analgesic effect. Single control (artificial cerebrospinal fluid) injections in PAG or PGC were without effect. The hyperalgesic effect of PAG tetracaine supports the involvement of PAG in normally occurring, tonic descending pain inhibition. The block of PGC met-enkephalin analgesia by distant injection of tetracaine in PAG supports the necessity of PAG integrity for PGC analgesic function.

Two separate studies were done on two sets of rats (33 rats, 101 cells in Expt. 1; 16 rats, 25 cells in Expt. 2). In the first study trigeminal nuclear neurons were categorized by adequate stimulus and receptive field. A total of 43.6% responded to light touch and noxious (pinch and heat) stimulation; 27.7% responded only to noxious pinch and/or heat; 8.9% responded exclusively to innocuous touch, and the remainder were non-responsive. Ninety percent of the responsive cells showed increased discharge rates in response to noxious stimulation. In the second study, after characterization of response properties, single nanoinjections of Met-enkephalin (ME) were separately made into midbrain periaqueductal gray (PAG) and nucleus reticularis paragigantocellularis (PGC). The effects of ME on spontaneous (SD) and evoked (ED) discharge were assessed, and then in 8 cells, the effects were repeated and successfully challenged with naloxone. The major findings were: (1) ME applied either to PAG or PGC causes naloxone-reversible reduction of noci-evoked ED with no effect on SD; and (2) the responses of neurons to innocuous light touch were unaffected by ME.

Unlabelled: Neuronal activity classified by receptive field, adequate stimulus, and raphe-spinal (R-S) projection in 48 lightly anaesthetized rats was recorded from raphe magnus (RM) area. Effects of nanoinjections of Met-enkephalin in periaqueductal gray (PAG; 2 or 10 micrograms), nucleus reticularis paragigantocellularis (PGC; 1 or 5 micrograms), and both sites (conjointly) were studied. Most of the 78 neurons studied responded to noxious stimulation, some with increased responses ('on-cells') and some with decreased responses ('off-cells')., Major Findings: (1) Met-enkephalin in PAG and PGC depressed the response of on-cells and enhanced the response of off-cells; (2) for a given RM or R-S cell, PAG and PGC effects were typically identical; and (3) conjoint injections tended to produce greater effects than single effects, whether enhancing or depressing.