Functional properties of dorsal horn neurons that project to the dorsal accessory olive.

1. This study examined the responses to natural cutaneous stimuli of neurons in the dorsal horn of the lumbosacral spinal cord that project to the dorsal accessory portion of the inferior olive (DAO) in cats anesthetized with pentobarbital sodium. Extracellular activity was recorded from single units antidromically activated by currents of less than or equal to 70 muA applied to DAO. 2. A total of 119 antidromically activated neurons was examined. Their antidromic activation latencies displayed a wide range (2.5-24.6 ms). The average latency corresponds to a conduction velocity of 24 m/s. 3. Collision was demonstrated for 24 neurons. All responded to some form of natural cutaneous stimulation. Their receptive fields encompassed some portion of the hind limb, particularly the toes; one-third displayed gradients of sensitivity. 4. Based on their thresholds to peripheral stimulation, the 24 neurons fell into five categories, those sensitive to light cutaneous stimuli (i.e., hair movement or light touch; 37.5%), rub (21%), tap (21%), pressure (12.5%), or noxious stimuli (8%). 5. Comparison of these results with data on the other major source of somatosensory information for DAO, the gracile nucleus (examined previously with the same methods), suggests that the sensitivity of neurons in DAO to light cutaneous stimuli is mediated primarily by neurons in the dorsal horn. The sensitivity of neurons in DAO to tap, rub, or pressure, on the other hand, might be mediated by neurons in either the dorsal horn, the gracile nucleus, or both.

A 5-HT1-type receptor mediates the antinociceptive effect of nucleus raphe magnus stimulation in the rat.

The serotonin-containing raphe-spinal pathway has been implicated as playing an important role in analgesia. Several studies, however, have reported the inefficacy of traditional serotonin receptor antagonists at reversing the antinociceptive action of electrical stimulation in the raphe. In the light of recent reports on the existence of several types of 5-HT receptors in rat spinal cord, the present study investigated the ability of two antagonists, selective for two different 5-HT receptors to reverse the effects of focal electrical stimulation of the raphe magnus nucleus in the rat. Electrical stimulation of this nucleus resulted in selective antinociceptive as well as non-selective inhibitory effects on dorsal horn neurones. Both these effects were blocked by the ionophoretic application of a 5-HT1, but not a 5-HT2 receptor antagonist. The study presents data supporting the role of a spinal 5-HT receptor in mediating stimulation-produced analgesia from the nucleus raphe magnus and further, furnishes evidence that the 5-HT1 receptor is involved in antinociception at the spinal level.

The involvement of neurokinin receptor subtypes in somatosensory processing in the superficial dorsal horn of the cat.

As well as substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) have recently been found in the superficial dorsal horn of the spinal cord; NKA originating mainly in fine primary afferents. We have investigated the effects of these tachykinins and a range of analogues on somatosensory responses of single identified dorsal horn neurons, when applied ionophoretically to the region of the substantia gelatinosa. Behavioural reflex tests of thermal nociception were carried out in parallel. The role of NK-1, NK-2 and NK-3 receptors was addressed. NK-1-selective agonists attenuated the non-nociceptive responses of identified multireceptive spinocervical tract (SCT) neurons. Of the endogenous tachykinins, both SP and NKB (a weak NK-1 agonist) showed this effect. No role for NK-3 receptors was identified in our experiments. NK-2-selective agonists (including NKA) caused a unique and selective facilitation of thermal nociceptive responses. NKA also reduced reflex response latency in tail-flick and hot plate tests. NKA as a primary afferent transmitter may thus be involved in mediating or facilitating the expression of thermal nociceptive inputs in the substantia gelatinosa. NKA and SP could be considered as acting in concert in the superficial dorsal horn in an effectively pro-nociceptive modulatory role. Evidence from receptor-selective antagonists supports that obtained with agonists for the roles of particular NK receptors in somatosensory processing. NK-2, but not NK-1 or NK-3 antagonists attenuated endogenous thermal nociceptive responses, supporting the hypothesis that an NK-2 agonist (such as NKA) may normally participate in expression of thermal nociception in the superficial dorsal horn. Behavioural experiments showing increased response latencies with a putative NK-2 selective antagonist further supported the involvement of NK-2 receptors in thermal nociception.

Heterogeneous effects of serotonin in the dorsal horn of rat: the involvement of 5-HT1 receptor subtypes.

The effect of ionophoretically applied serotonin (5-HT) was tested on cutaneous sensory responses of multireceptive dorsal horn neurones in the anaesthetized rat. Three types of 5-HT action were discerned: selective inhibition of nociceptive responses (10/18 cells), non-selective inhibition of responses to both noxious and innocuous stimuli as well as to excitatory amino acids (4/18 cells) and non-selective excitation of evoked responses (1/18 cells). A few cells (3/18) were unaffected by 5-HT. The use of agonists, shown to discriminate between subtypes of 5-HT1 receptor revealed that a 5-HT1A receptor agonist mimicked the non-selective effects of 5-HT, whereas a 5-HT1B receptor agonist mimicked the selective antinociceptive effects of 5-HT. A 5-HT2 receptor agonist, in contrast, was without effect. Both the selective and the non-selective effects were reversed by a 5-HT1 receptor antagonist, but not a 5-HT2 antagonist.

The influence of opioid receptor subtypes on the processing of nociceptive inputs in the spinal dorsal horn of the cat.

Extracellular recordings were made of the cutaneous sensory responses of spinocervical tract (SCT) neurones in the lumbar dorsal horn of anaesthetised and paralysed cats. All of the neurones studied were multireceptive, showing excitatory responses to both innocuous and noxious (thermal and when tested, mechanical) stimuli applied to their cutaneous receptive fields on the ipsilateral hindlimb. The effects of iontophoretically applied opioids were studied on a regular cycle of responses to these cutaneous stimuli and also to D.L-homocysteic acid (DLH). In the first series of experiments, drugs were applied in the vicinity of the SCT neurones. The kappa-receptor agonists dynorphin A(1-13) and U50488H, but not dynorphin A(2-13), the mu-agonist DAGO, or the delta-agonist DADL, caused a selective reduction of the nociceptive responses of the neurones. The corresponding responses to innocuous stimuli or to DLH, and spontaneous activity were unaffected. In the second series of experiments, drugs were applied from a second electrode placed in the region of the substantia gelatinosa directly dorsal to the tip of the recording electrode. Under these conditions, the mu-receptor agonist DAGO, but not the kappa-agonist dynorphin A(1-13) or the delta-agonists DADL, DSLET or DLPEN, showed a selective antinociceptive effect. In both series, the antinociceptive effects of the opioids were readily reversed by iontophoretically applied naloxone. The effect of dynorphin A(1-13) applied close to SCT neurones, but not that of DAGO applied in the region of the substantia gelatinosa, was reversed by the alpha 2-adrenoceptor antagonist, idazoxan. The results indicate that both mu- and kappa-opioid receptors (at anatomically distinct sites) can participate in the selective antinociceptive influence that opioids can exert over somatosensory information ascending to supraspinal levels. The antagonism of kappa-receptor-mediated antinociception by idazoxan is consistent with an interaction of opioid and noradrenaline influences at the level of the dorsal horn.