Convergent Cutaneous Receptive Fields Research Articles

Local group I mGluR antagonists reduce TMJ-evoked activity of trigeminal subnucleus caudalis neurons in female rats

Group I metabotropic glutamate receptors (mGluR1 and mGluR5) are functionally linked to estrogen receptors and play a key role in the plasticity of central neurons. Estrogen status strongly influences sensory input from the temporomandibular joint (TMJ) to neurons at the spinomedullary (Vc/C1–2) region. This study tested the hypothesis that TMJ input to trigeminal subnucleus caudalis/upper cervical cord (Vc/C1–2) neurons involved group I mGluR activation and depended on estrogen status. TMJ-responsive neurons were recorded in superficial laminae at the Vc/C1–2 region in ovariectomized (OvX) female rats treated with low-dose estradiol (2μg/day, LE) or high-dose estradiol (20μg/day, HE) for 2days. TMJ-responsive units were activated by adenosine triphosphate (ATP, 1mM) injected into the joint space. Receptor antagonists selective for mGluR1 (CPCCOEt) or mGluR5 (MPEP) were applied topically to the Vc/C1–2 surface at the site of recording 10min prior to the intra-TMJ ATP stimulus. In HE rats, CPCCOEt (50 and 500μM) markedly reduced ATP-evoked unit activity. By contrast, in LE rats, a small but significant increase in neural activity was seen after 50μM CPCCOEt, while 500μM caused a large reduction in activity that was similar in magnitude as that seen in HE rats. Local application of MPEP produced a significant inhibition of TMJ-evoked unit activity independent of estrogen status. Neither mGluR1 nor mGluR5 antagonism altered the spontaneous activity of TMJ units in HE or LE rats. High-dose MPEP caused a small reduction in the size of the convergent cutaneous receptive field in HE rats, while CPCCOEt had no effect. These data suggest that group I mGluRs play a key role in sensory integration of TMJ nociceptive input to the Vc/C1–2 region and are largely independent of estrogen status.

Inhibition of temporomandibular joint input to medullary dorsal horn neurons by 5HT3 receptor antagonist in female rats

Repeated forced swim (FS) conditioning enhances nociceptive responses to temporomandibular joint (TMJ) stimulation in female rats. The basis for FS-induced TMJ hyperalgesia remains unclear. To test the hypothesis that serotonin 3 receptor (5HT3R) mechanisms contribute to enhanced TMJ nociception after FS, ovariectomized female rats were treated with estradiol and subjected to FS for three days. On day 4, rats were anesthetized with isoflurane and TMJ-responsive neurons were recorded from superficial and deep laminae at the trigeminal subnucleus caudalis/upper cervical (Vc/C1–2) region and electromyographic (EMG) activity was recorded from the masseter muscle. Only Vc/C1–2 neurons activated by intra-TMJ injections of ATP were included for further analysis. Although neurons in both superficial and deep laminae were activated by ATP, only neurons in deep laminae displayed enhanced responses after FS. Local application of the 5HT3R antagonist, ondansetron (OND), at the Vc/C1–2 region reduced the ATP-evoked responses of neurons in superficial and deep laminae and reduced the EMG response in both sham and FS rats. OND also decreased the spontaneous firing rate of neurons in deep laminae and reduced the high-threshold convergent cutaneous receptive field area of neurons in superficial and deep laminae in both sham and FS rats. These results revealed that central application of a 5HT3R antagonist, had widespread effects on the properties of TMJ-responsive neurons at the Vc/C1–2 region and on jaw muscle reflexes under sham and FS conditions. It is concluded that 5HT3R does not play a unique role in mediating stress-induced hyperalgesia related to TMJ nociception.

Posterior hypothalamic modulation of ocular-responsive trigeminal subnucleus caudalis neurons is mediated by Orexin-A and Orexin1 receptors.

Orexin-A (OxA) is synthesized in posterior and lateral regions of the hypothalamus and contributes to homeostatic regulation of body functions including pain modulation. To determine if orexinergic mechanisms contribute to posterior hypothalamus (PH)-induced modulation of ocular input to subnucleus caudalis/upper cervical (Vc/C1) neurons, the orexin-1 receptor antagonist SB334867 was applied to the dorsal brainstem surface prior to PH disinhibition, by bicuculline methiodide, in male rats under isoflurane anesthesia. Ocular input to Vc/C1 units by bright light or hypertonic saline was markedly reduced by PH disinhibition and reversed completely by local Vc/C1 application of SB334867. OxA applied to the Vc/C1 surface mimicked the effects of PH disinhibition in a dose-dependent manner. OxA-induced inhibition was prevented by co-application of SB334867, but not by the orexin-2 receptor antagonist TCS Ox2 29. PH disinhibition and local OxA application also reduced the high threshold convergent cutaneous receptive field area of ocular units, suggesting widespread effects on somatic input to Vc/C1 ocular units. Vc/C1 application of OxA or SB334867 alone did not affect the background discharge of ocular units and suggested that the PH-OxA influence on ocular unit activity was not tonically active. Vc/C1 application of OxA or SB334867 alone also did not alter mean arterial pressure, whereas PH disinhibition evoked prompt and sustained increases. These results suggest that stimulus-evoked increases in PH outflow acts through OxA and orexin-1 receptors to alter the encoding properties of trigeminal brainstem neurons responsive to input from the ocular surface and deep tissues of the eye.

GABAergic influence on temporomandibular joint-responsive spinomedullary neurons depends on estrogen status

Sensory input from the temporomandibular joint (TMJ) to neurons in superficial laminae at the spinomedullary (Vc/C1–2) region is strongly influenced by estrogen status. This study determined if GABAergic mechanisms play a role in estrogen modulation of TMJ nociceptive processing in ovariectomized female rats treated with high- (HE) or low-dose (LE) estradiol (E2) for 2days. Superficial laminae neurons were activated by ATP (1mM) injections into the joint space. The selective GABAA receptor antagonist, bicuculline methiodide (BMI, 5 or 50μM, 30μl), applied at the site of recording greatly enhanced the magnitude and duration of ATP-evoked responses in LE rats, but not in units from HE rats. The convergent cutaneous receptive field (RF) area of TMJ neurons was enlarged after BMI in LE but not HE rats, while resting discharge rates were increased after BMI independent of estrogen status. By contrast, the selective GABAA receptor agonist, muscimol (50μM, 30μl), significantly reduced the magnitude and duration of ATP-evoked activity, resting discharge rate, and cutaneous RF area of TMJ neurons in LE and HE rats, whereas lower doses (5μM) affected only units from LE rats. Protein levels of GABAA receptor β3 isoform at the Vc/C1–2 region were similar for HE and LE rats. These results suggest that GABAergic mechanisms contribute significantly to background discharge rates and TMJ-evoked input to superficial laminae neurons at the Vc/C1–2 region. Estrogen status may gate the magnitude of GABAergic influence on TMJ neurons at the earliest stages of nociceptive processing at the spinomedullary region.

Posterior hypothalamic modulation of light-evoked trigeminal neural activity and lacrimation

Enhanced light sensitivity is a common feature of many neuro-ophthalmic conditions and some chronic headaches. Previously we reported that the bright light-evoked increases in trigeminal brainstem neural activity and lacrimation depended on a neurovascular link within the eye (Okamoto et al., 2012). However, the supraspinal pathways necessary for these light-evoked responses are not well defined. To assess the contribution of the posterior hypothalamic area (PH), a brain region closely associated with control of autonomic outflow, we injected bicuculline methiodide (BMI), a GABAa receptor antagonist, into the PH and determined its effect on the encoding properties of ocular neurons at the ventrolateral trigeminal interpolaris/caudalis transition (Vi/Vc) and caudalis/upper cervical cord junction (Vc/C1) regions and on reflex lacrimation in male rats under isoflurane anesthesia. BMI markedly reduced light-evoked (>80%) responses of Vi/Vc and Vc/C1 neurons at 10min with partial recovery by 50min after injection. BMI also reduced (>35%) the convergent cutaneous receptive field area of Vi/Vc and Vc/C1 ocular neurons indicating that both intra-ocular and periorbital cutaneous inputs were affected by changes in PH outflow. Light-evoked lacrimation was reduced by >35% at 10min after BMI, while resting mean arterial pressure increased promptly and remained elevated (>20mmHg) throughout the 50-min post-injection period. These results suggested that PH stimulation, acting in part through increased sympathetic activity, significantly inhibited light- and facial skin-evoked activity of ocular neurons at the Vi/Vc and Vc/C1 region. These data provide further support for the hypothesis that autonomic outflow plays a critical role in mediating light-evoked trigeminal brainstem neural activity and reflex lacrimation.

Behavioral and neurophysiological correlates of nociception in an animal model of photokeratitis

Ocular exposure to ultraviolet irradiation (UVR) induces photokeratitis, a common environmental concern that inflames ocular tissues and causes pain. The central neural mechanisms that contribute to the sensory aspects of photokeratitis after UVR are not known. In awake male rats, ocular surface application of hypertonic saline evoked eye wipe behavior that was enhanced 2–3 days after UVR and returned to control levels by 7 days. Similarly, under isoflurane anesthesia, hypertonic saline-evoked activity of ocular neurons in superficial laminae at the trigeminal subnucleus caudalis/cervical (Vc/C1) region was enhanced 2 days, but not 7 days, after UVR. By contrast, the response of neurons at the interpolaris/caudalis (Vi/Vc) transition region to hypertonic saline was not affected by UVR. The background activity and convergent cutaneous receptive field areas of Vc/C1 or Vi/Vc neurons were not affected by UVR. Aqueous humor protein levels were elevated 2 and 7 days after UVR. UVR enhanced nociceptive behavior, after a latent period, with a time course similar to that of ocular neurons in superficial laminae at the Vc/C1 region. The Vc/C1 region plays a key role in primary hyperalgesia induced by UVR, whereas the Vi/Vc region likely mediates other aspects of ocular function.

NMDA receptor blockade reduces temporomandibular joint-evoked activity of trigeminal subnucleus caudalis neurons in an estrogen-dependent manner

Estrogen status is a risk factor in painful temporomandibular disorders (TMJD). Previously we reported that estradiol (E2) enhanced nociceptive processing of TMJ input by neurons in superficial laminae at the spinomedullary (Vc/C1-2) region; however, the mechanisms for this enhancement are not known. The present study determined if ionotropic glutamate receptors contribute to TMJ nociceptive processing in an E2-dependent manner. Ovariectomized (OvX) female rats were treated with high E2 (HE2) or low dose E2 (LE2) for 2 days and neural activity was recorded in laminae I–II at the Vc/C1-2 region. TMJ-responsive units were activated by ATP injections into the joint space. ATP-evoked unit responses in HE2 rats were reduced significantly by topical application of the N-methyl-d-aspartate receptor antagonist, d(−)-2-amino-5-phosphonopentanoic acid (AP5) in a dose-related manner, while units from LE2 were not affected. Application of the non-NMDA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), inhibited the ATP-evoked responses in both groups. Spontaneous activity of TMJ units was not influenced by AP5, whereas it was reduced by DNQX similarly in both groups. The high threshold convergent cutaneous receptive field area of TMJ units was not changed by AP5, whereas DNQX caused a significant reduction in both groups. These results suggest that NMDA-dependent mechanisms contribute to the enhanced ATP-evoked responses of TMJ units in superficial laminae at the Vc/C1-2 region under high E2 conditions, while non-NMDA-dependent mechanisms modify the encoding properties of TMJ units independent of E2 status.

Endotoxin-Induced Uveitis Causes Long-Term Changes in Trigeminal Subnucleus Caudalis Neurons

Endotoxin-induced uveitis (EIU) is commonly used in animals to mimic ocular inflammation in humans. Although the peripheral aspects of EIU have been well studied, little is known of the central neural effects of anterior eye inflammation. EIU was induced in male rats by endotoxin or lipopolysaccharide (LPS, 1 mg/kg ip) given 2 or 7 days earlier. Neurons responsive to mechanical stimulation of the ocular surface were recorded under barbiturate anesthesia at the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/cervical cord (Vc/C1) junction, the main terminal regions for corneal nociceptors. Two days after LPS, Vc/C1 units had reduced responses to histamine, nicotine, and CO(2) gas applied to the ocular surface, whereas unit responses were increased 7 days after LPS. Those units with convergent cutaneous receptive fields at Vc/C1 were enlarged 7 days after LPS. Units at the Vi/Vc transition also had reduced responses to histamine and CO(2) 2 days after LPS but no enhancement was seen at 7 days. Tear volume evoked by CO(2) was reduced 2 days after LPS and returned toward control values by 7 days, whereas CO(2)-evoked eye blinks were normal at 2 days and increased 7 days after LPS. These results indicate that a single exposure to endotoxin causes long-term changes in the excitability of second-order neurons responsive to noxious ocular stimulation. The differential effects of EIU on tear volume and eye blink lend further support for the hypothesis that ocular-sensitive neurons at the Vi/Vc transition and Vc/C1 junction regions mediate different aspects of pain during intraocular inflammation.

Differential modulation of TMJ neurons in superficial laminae of trigeminal subnucleus caudalis/upper cervical cord junction region of male and cycling female rats by morphine

Sex differences in the cellular responses to morphine were examined in an animal model of temporomandibular joint (TMJ) pain. TMJ-responsive neurons were recorded in the superficial laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C 2) junction region, the initial site of synaptic integration for TMJ afferents, in male and cycling female rats under barbiturate anesthesia. Unit activity was evoked by local injection of bradykinin into the TMJ capsule at 30 min intervals and the effects of morphine sulfate (0.03–3 mg/kg, i.v.) were assessed by a cumulative dose regimen. Morphine caused a dose-related inhibition of bradykinin-evoked unit activity in males and diestrous females in a naloxone-reversible manner, while evoked unit activity in proestrous females was not reduced. The apparent sex hormone-related aspect of morphine analgesia was selective for evoked unit activity, since the spontaneous activity of TMJ units was reduced similarly in all groups, while the convergent cutaneous receptive field area of TMJ units did not change in any group. These results were consistent with the hypothesis that sex hormone status interacts with pain control systems to modify neural activity at the level of the Vc/C 2 junction region relevant for TMD pain.

Evidence for two populations of rat spinal dorsal horn neurons excited by urinary bladder distension

Spinal L6-S2 dorsal horn neurons of cervical spinal cord-transected, decerebrate female rats were characterized using urinary bladder distension (UBD) as a visceral stimulus. Constant pressure, phasic, graded (20–80 mm Hg, 20 s) air UBD was delivered via a transurethral catether and extracellular single-unit recordings obtained from all neurons excited by UBD. Responses to graded UBD and noxious/non-noxious cutaneous stimuli were determined in 258 neurons which could be stratified into two groups based on their effect of a counterirritation stimulus: Type I neurons (n=112) were inhibited by noxious pinch presented in a non-segmental field; Type II neurons (n=146) were not similarly inhibited. Both Types of neurons were identified in both superficial and deep recording sites and demonstrated graded responses to graded UBD. All UBD-excited neurons had convergent cutaneous receptive fields (RFs) excited by non-noxious and/or noxious stimuli. As a group, Type I neurons had a period of decreased activity following termination of the distending stimulus whereas Type II neurons typically had a sustained afterdischarge. UBD-evoked activity in Type II neurons was inhibited more than similar activity in Type I neurons by both intravenous morphine and lidocaine. These results support the assertion that at least two different populations of spinal dorsal horn neurons exist which encode for a stimulus of urinary bladder distension. These populations are an analogue to previously characterized, similar neuronal populations excited by colorectal distension and suggest that they are representative of the overall phenomenon of visceral sensory processing, a component of which is nociception.

Parabrachial area and nucleus raphe magnus inhibition of corneal units in rostral and caudal portions of trigeminal subnucleus caudalis in the rat

The cornea has been used extensively as a means to selectively stimulate trigeminal nociceptive neurons. The aim of this study was to determine the effects of descending modulatory control pathways on corneal unit activity by comparing the effects of conditioning stimulation of the pontine parabrachial area (PBA CS) and nucleus raphe magnus (NRM CS). Electrical stimulation of the cornea at A- and C-fiber intensities was used to activate neurons in two regions of the trigeminal spinal nucleus, the subnucleus interpolaris/caudalis transition (Vi/Vc, ‘rostral units’) and laminae I–II at the subnucleus caudalis/cervical cord transition (Vc/C1, ‘caudal units’), in chloralose-anesthetized rats. Corneal units were further classified according to convergent cutaneous receptive field properties and PBA projection status. None of 48 rostral and 23/28 caudal units projected to the ipsilateral or contralateral PBA. PBA CS inhibited the cornea-evoked responses (<75% change from control) of approximately 65% of rostral and caudal units regardless of neuronal class. For rostral corneal units, PBA CS inhibited A- and C-fiber input equally (15±3 and 18±14% of control, respectively), whereas among caudal units, A-fiber input was inhibited more than C-fiber input (26±5 and 64±12% of control, respectively, P<0.01). The magnitude of NRM CS inhibition on cornea-evoked activity of both rostral and caudal units was not different from that seen after PBA CS. Glutamate microinjections into PBA also inhibited rostral and caudal corneal units (6/9 tested). These results indicate that corneal input to rostral and caudal units is modified by activation of descending controls from the PBA and NRM. The significance for processing corneal sensory information is discussed in terms of functional differences between rostral and caudal neurons.

The effect of fentanyl, DNQX and MK-801 on dorsal horn neurones responsive to colorectal distension in the anaesthetized rat.

Certain dorsal horn neurones respond in a graded manner to noxious colorectal distension (CRD). Morphine inhibits these responses in the spinalized rat, but the role of excitatory amino acids in baseline visceral nociceptive transmission is less clear. This study examines the effect of the mu-opiate receptor agonist fentanyl, and the non-NMDA and NMDA antagonists DNQX and MK-801, respectively, on such responses to CRD in the sodium pentobarbitone-anaesthetized rat. Male rats were prepared for extracellular recording from the lumbosacral spinal cord. 90 neurones responsive to CRD, located throughout the dorsal horn, were classified according to their response duration and latency to 60 mmHg distension, as SL-A (short latency-abrupt; 59%), SL-S (short latency-sustained; 23%), L-L (long-latency; 10%) and Inhib (inhibited; 8%). Convergent cutaneous receptive fields were mapped for 79/90 neurones and classified as LT (low threshold), WDR (wide dynamic range) or HT (high threshold). CRD (20-100 mm Hg) elicited graded responses in most neurones. In 6/6 SL-S neurones, fentanyl (1-8 microg kg-1) dose-dependently inhibited the response to 60 mm Hg CRD, in a naloxone-sensitive manner, with an ID50 value (+/-95% confidence limits) of 2.48 (1.7-3. 7) microg kg-1. In 6/6 SL-A neurones, fentanyl had no significant effect on the response to CRD. DNQX (0.03-3 mg kg-1) produced a dose-dependent inhibition of the response to CRD in 5/5 SL-A neurones, with an ID50 value of 0.32 (0.01-41.1) mg kg-1. MK-801 (0. 03-0.3 mg kg-1) had no significant effect on responses to CRD in 6/6 SL-A neurones. The differential inhibitory effects of fentanyl on two neuronal subtypes may indicate functional differences. In SL-A neurones AMPA/kainate, but not NMDA receptors are involved in mediating baseline nociceptive neurotransmission.

Responses of medullary dorsal horn neurons to corneal stimulation by CO(2) pulses in the rat.

Corneal-responsive neurons were recorded extracellularly in two regions of the spinal trigeminal nucleus, subnucleus interpolaris/caudalis (Vi/Vc) and subnucleus caudalis/upper cervical cord (Vc/C1) transition regions, from methohexital-anesthetized male rats. Thirty-nine Vi/Vc and 26 Vc/C1 neurons that responded to mechanical and electrical stimulation of the cornea were examined for convergent cutaneous receptive fields, responses to natural stimulation of the corneal surface by CO(2) pulses (0, 30, 60, 80, and 95%), effects of morphine, and projections to the contralateral thalamus. Forty-six percent of mechanically sensitive Vi/Vc neurons and 58% of Vc/C1 neurons were excited by CO(2) stimulation. The evoked activity of most cells occurred at 60% CO(2) after a delay of 7-22 s. At the Vi/Vc transition three response patterns were seen. Type I cells (n = 11) displayed an increase in activity with increasing CO(2) concentration. Type II cells (n = 7) displayed a biphasic response, an initial inhibition followed by excitation in which the magnitude of the excitatory phase was dependent on CO(2) concentration. A third category of Vi/Vc cells (type III, n = 3) responded to CO(2) pulses only after morphine administration (>1.0 mg/kg). At the Vc/C1 transition, all CO(2)-responsive cells (n = 15) displayed an increase in firing rates with greater CO(2) concentration, similar to the pattern of type I Vi/Vc cells. Comparisons of the effects of CO(2) pulses on Vi/Vc type I units, Vi/Vc type II units, and Vc/C1 corneal units revealed no significant differences in threshold intensity, stimulus encoding, or latency to sustained firing. Morphine (0.5-3.5 mg/kg iv) enhanced the CO(2)-evoked activity of 50% of Vi/Vc neurons tested, whereas all Vc/C1 cells were inhibited in a dose-dependent, naloxone-reversible manner. Stimulation of the contralateral posterior thalamic nucleus antidromically activated 37% of Vc/C1 corneal units; however, no effective sites were found within the ventral posteromedial thalamic nucleus or nucleus submedius. None of the Vi/Vc corneal units tested were antidromically activated from sites within these thalamic regions. Corneal-responsive neurons in the Vi/Vc and Vc/C1 regions likely serve different functions in ocular nociception, a conclusion reflected more by the difference in sensitivity to analgesic drugs and efferent projection targets than by the CO(2) stimulus intensity encoding functions. Collectively, the properties of Vc/C1 corneal neurons were consistent with a role in the sensory-discriminative aspects of ocular pain due to chemical irritation. The unique and heterogeneous properties of Vi/Vc corneal neurons suggested involvement in more specialized ocular functions such as reflex control of tear formation or eye blinks or recruitment of antinociceptive control pathways.

Modulation of spinal visceral nociceptive transmission by NMDA receptor activation in the rat.

1. Thirty-three neurons in the L6-Sl spinal cord of 30 adult male Sprague-Dawley rats were characterized for responses to colorectal distention (CRD, 20-80 mmHg, 20 s) and convergent cutaneous receptive fields in the presence and absence of N-methyl-D-aspartate (NMDA; 1 microM) or D-serine (1 microM) administered locally by pressure ejection. 2. NMDA ejected locally increased the resting (spontaneous) activity, responses to CRD, postdistention afterdischarges, encoding of visceral nociception, and the size of convergent cutaneous receptive fields of some neurons. Facilitation of responses to noxious intensities of CRD (> or = 40 mmHg) was apparent between 30 s and 4 min after drug ejection. The slope of stimulus-response functions to graded intensities of CRD was increased significantly by NMDA, although mean response threshold was not significantly altered after NMDA ejection. 3. Facilitatory effects of NMDA on responses to CRD and increases in size of convergent cutaneous receptive fields were blocked or reversed by administration of the NMDA receptor antagonist, 5-amino-2-phosphono-valeric acid. 4. D-serine, an agonist at the glycine modulatory site on the NMDA receptor complex, generally mimicked the effects of NMDA on neurons responsive to CRD. The effects of D-serine were blocked by the glycine site antagonist 7-chloro-kynurenic acid (7-CK). 7-CK also blocked NMDA-produced effects on responses to CRD and increases in size of cutaneous receptive fields. 5. No differences were found between spinal neurons with and without documented long ascending projections with respect to effects of NMDA or D-serine. 6. These findings demonstrate involvement of spinal NMDA receptors in mediating hyperexcitability of spinal neurons to visceral nociceptive input and suggest an important contribution of spinal NMDA receptors in visceral hyperalgesic syndromes.

Interactions between visceral and cutaneous nociception in the rat. I. Noxious cutaneous stimuli inhibit visceral nociceptive neurons and reflexes

1. Numerous studies have demonstrated that neural, behavioral, and reflex responses to a nociceptive test stimulus are inhibited by conditioning nociceptive stimuli; this inhibition has supraspinal, intraspinal, and segmental components. The general phenomenon is defined here as nocigenic inhibition. The present study of nocigenic inhibition documents that noxious cutaneous pinch and heat, used as conditioning stimuli, inhibit neuronal and reflex responses evoked by a noxious visceral stimulus, colorectal distension. 2. A total of 196 dorsal horn neurons were examined: 110 were short latency-abrupt (SL-A) neurons that were excited at short latency by colorectal distension and returned to baseline activity abruptly after termination of the distending stimulus, and 86 were short latency-sustained (SL-S) neurons that also were excited by colorectal distension at short latency, but demonstrated after-discharges for 4-240 s after termination of the distending stimulus. All SL-A and SL-S neurons studied had convergent cutaneous receptive fields. 3. The spontaneous activities of 100% of the 110 SL-A neurons tested were inhibited by greater than 25% by noxious pinch in sites distant from their convergent cutaneous receptive fields. In both anesthetized, intact, and spinalized rats, noxious conditioning pinch or noxious conditioning heat significantly reduced responses of SL-A neurons during noxious test colorectal distension. The magnitude of this nocigenic inhibition was graded with the intensity of the noxious conditioning stimulus. Noxious conditioning tail heating produced a parallel shift to the right in stimulus-response functions relating neuronal responses to the intensity of colorectal distension (20-100 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Purkinje cell simple spike activity during grasping and lifting objects of different textures and weights

1. Three monkeys (2.5-3.5 kg) were trained to pinch an object between the thumb and forefinger and to lift it a vertical distance of 1.0-2.0 cm. Either the object weight (15, 65, or 115 g) or the surface texture (sand paper or polished metal) contacting the fingers could be varied. The object was equipped with a vertical position transducer, an accelerometer, and strain gauges that measured the grip force and the vertical load force. 2. In accordance with similar previously published studies on human subjects, it was found that monkeys appropriately scaled the grip forces according to the weight and coefficient of friction of the object. The grip force preceded the load force by 25 ms, and they both covaried with the changes in surface friction. 3. An analysis of electromyograms (EMGs) recorded intramuscularly from the muscles of the wrist and fingers including both flexors and extensors indicated that 26 muscles were active during pinching and lifting. Of these, 17 produced the maximum activity for the slippery surface and the greatest weight and the least activity with the roughest surface and lightest weight. 4. A total of 59 Purkinje cells and 123 unidentified units recorded from the paravermal and lateral cerebellar cortex were found to change their firing frequency during lifting the experimental object. 5. Increased discharge during the grasping and lifting was found for 56% (33/59) of the Purkinje cells and 80% (98/123) of the unidentified neurons, whereas 44% (26/59) of the Purkinje cells and 20% of the unidentified neurons decreased activity during the same period. 6. Significant modulations of the firing frequency with surface texture or object weight occurred for 59% (35/59) of the Purkinje cells and 67% (82/123) of the unidentified neurons. 7. One hundred and three Purkinje and unidentified neurons recorded in the paravermal and lateral region of the cerebellar cortex were examined for peripheral receptive fields, and of these, 43/103 (42%) responded exclusively to imposed displacements and tapping of muscles suggesting afferents originating from proprioceptors. A further 28/103 (27%) had exclusively cutaneous receptive fields on the hand that could be stimulated by brushing the skin lightly with a sable hair brush. Only six neurons demonstrated convergent cutaneous and proprioceptive receptive fields and no response to peripheral stimulation could be found for 26 neurons. No difference was found between the receptive fields of Purkinje cells and those of the unidentified neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization of superficial T 13-L 2 dorsal horn neurons encoding for colorectal distension in the rat: comparison with neurons in deep laminae

Fifty-five neurons responsive to colorectal distension located in the superficial spinal dorsal horn (0.0–0.3 mm ventral to the cord dorsum) of the T 13-L 2 spinal segments of pentobarbital-anesthetized, physiologically intact or spinalized (C 1 transection), decerebrate rats were characterized. These neurons could be separated into three groups based upon their response to an 80 mm Hg, 20 s colorectal distension: (1) short latency-abrupt (SL-A) neurons ( n = 22) that were excited by colorectal distension at a short latency (<1s) and abruptly terminated responses following the termination of the distending stimulus; (2) short latency-sustained (SL-S) neurons ( n = 26) that were excited by colorectal distension at a short latency (<1s) and demonstrated sustained responses (<4s) following termination of the distending stimulus; and (3) INHIB neurons ( n = 7) that were spontaneously active and were inhibited by colorectal distension. All 55 neurons had convergent cutaneous receptive fields (i.e. were ‘viscerosomatic’), exhibiting excitatory responses to noxious (pinch/heat) and/or non-noxious (brush) stimuli. Neurons excited by colorectal distension also demonstrated monotonic, accelerating responses to graded colorectal distension, were excited by the intraarterial administration of bradykinin, could be antidromically activated by electrical stimulation in the caudal ventrolateral medulla and were subject to tonic descending inhibitory modulation as evidenced by more vigorous responses to distension when rats were reversibly spinalized using a cold block. A comparison of these 55 superficial dorsal horn neurons with 90 neurons located in the deep spinal dorsal horn (0.4–1.3 mm ventral to the cord dorsum) demonstrated quantitative differences between SL-A neurons located superficially and those located at deeper sites; no quantitative differences between respective groups of SL-S and INHIB neurons were apparent.

Characterization of neurons responsive to noxious colorectal distension in the T13-L2 spinal cord of the rat.

1. One-hundred thirty-two neurons responsive to colorectal distension in the dorsal horn of the T13-L2 spinal segments of 35 spinalized and 7 intact, deeply pentobarbital-sodium-anesthetized rats were characterized for convergent cutaneous receptive fields, long ascending projections and responses to the intra-arterial administration of the algesic peptide bradykinin. All but 9 neurons had an identifiable excitatory cutaneous receptive field; all receptive fields were located on the lower abdomen, flank, and dorsal body surface. Electrical stimulation in the cutaneous fields of 28 neurons demonstrated that neurons responsive to colorectal distension receive afferent information carried by A- and C-fibers. Stimulus-response functions (SRFs) of 52 neurons excited by graded colorectal distension (20-100 mmHg, 20 s) were monotonic and accelerating, allowing extrapolation of threshold distending pressures to neuronal response. Neurons were subdivided into four classes based upon their response to an 80-mmHg, 20-s colorectal distension search stimulus. 2. Short-latency abrupt [SL-A] neurons (spinalized, n = 46; intact, n = 9) were excited at short latency; activity abruptly returned to base line on termination of distension. Six of 9 neurons in intact rats had long ascending projections as demonstrated by antidromic invasion from the contralateral, ventrolateral caudal medulla. Responses of SL-A neurons to colorectal distension were significantly greater in spinalized than in intact rats. Fifty-three of 55 SL-A neurons had convergent excitatory cutaneous receptive fields and most were responsive to both noxious and nonnoxious stimuli. Ten of 13 neurons tested were excited by intra-arterial bradykinin. The threshold distending pressure, determined from the SRFs of 29 neurons in both the spinalized and intact states, extrapolated to near 0 mmHg. 3. Short-latency sustained (SL-S) neurons (spinalized, n = 31; intact, n = 11) were also excited at short latency in response to colorectal distension, but responses were sustained for 4-50 s following termination of the distending stimulus. Nine of 11 SL-S neurons in intact rats had long ascending projections. All 42 SL-S neurons were spontaneously active and 41 of 42 had convergent excitatory cutaneous receptive fields, excited exclusively by noxious stimuli (n = 29) or excited by both noxious and nonnoxious stimuli (n = 12). Responses to colorectal distension and spontaneous activity were significantly greater in spinalized rats. Twelve of 12 neurons tested were excited by intra-arterial bradykinin.(ABSTRACT TRUNCATED AT 400 WORDS)