RESUMEN
Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain possibly through a neuroinflammatory response. NP sensitizes dorsal horn neuronal responses, but it is unknown whether this reflects a central or peripheral sensitization. To study central sensitization, we tested if NP enhances windup--the progressive increase in the response of a nociceptive spinal neuron to repeated electrical C-fiber stimulation--a phenomenon that may partly account for temporal summation of pain. Single-unit recordings were made from wide dynamic range (WDR; n = 36) or nociceptive-specific (NS; n = 8) L5 dorsal horn neurons in 44 isoflurane-anesthetized rats. Subcutaneous electrodes delivered electrical stimuli (20 pulses, 3 times the C-fiber threshold, 0.5 ms) to the receptive field on the hindpaw. Autologous NP was harvested from a tail disc and placed onto the L5 dorsal root ganglion after recording of baseline responses (n = 22). Controls had saline applied similarly (n = 22). Electrical stimulus trains (0.1, 0.3, and 1 Hz; 5-min interstimulus interval) were repeated every 30 min for 3-6 h after each treatment. The total number of evoked spikes (summed across all 20 stimuli) to 0.1 Hz was enhanced 3 h after NP, mainly in the after-discharge (AD) period (latency > 400 ms). Total responses to 0.3 and 1.0 Hz were also enhanced at > or = 60 min after NP in both the C-fiber (100- to 400-ms latency) and AD periods, whereas the absolute windup (C-fiber + AD - 20 times the initial response) increased at > or = 90 min after treatment. In saline controls, windup was not enhanced at any time after treatment for any stimulus frequency, although there was a trend toward enhancement at 0.3 Hz. These results are consistent with NP-induced central sensitization. Mechanical responses were not significantly enhanced after saline or NP treatment. We speculate that inflammatory agents released from (or recruited by) NP affect the dorsal root ganglion (and/or are transported to cord) to enhance primary afferent excitation of nociceptive dorsal horn neurons.
Asunto(s)
Ganglios Espinales/citología , Hiperalgesia/etiología , Disco Intervertebral/trasplante , Células del Asta Posterior/fisiopatología , Trasplante de Tejidos/efectos adversos , Potenciales de Acción/fisiología , Potenciales de Acción/efectos de la radiación , Animales , Región Lumbosacra , Masculino , Fibras Nerviosas/fisiología , Dimensión del Dolor/métodos , Estimulación Física/métodos , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Trasplante Autólogo/efectos adversosRESUMEN
BACKGROUND: Windup of spinal nociceptive neurones may underlie temporal summation of pain, influencing the minimum alveolar concentration (MAC) of anaesthetics required to prevent movement to supramaximal stimuli. We hypothesized that halothane and isoflurane would differentially affect windup of dorsal horn neurones. METHODS: We recorded 18 nociceptive dorsal horn neurones exhibiting windup to 1 Hz electrical hindpaw stimuli in rats. Effects of 0.8 and 1.2 MAC isoflurane and halothane were recorded in the same neurones (counterbalanced, crossover design). Windup was calculated as the total number of C-fibre (100-400 ms latency) plus afterdischarge (400-1000 ms latency) spikes/20 stimuli (area under curve, AUC) or absolute windup (C-fibre plus afterdischarge-20 x initial response). RESULTS: Increasing isoflurane from 0.8 to 1.2 MAC did not affect AUC, but increased absolute windup from 429 (62) to 618 (84) impulses/20 stimuli (P<0.05) and depressed the initial C-fibre response from 14 (3) to 8 (2) impulses (P<0.05). Increasing halothane from 0.8 to 1.2 MAC depressed AUC from 690 (79) to 537 (65) impulses/20 stimuli (P<0.05) and the initial response from 18 (2) to 13 (2) impulses (P<0.05), but absolute windup was not affected. Absolute windup was 117% greater during 1.2 MAC isoflurane compared with 1.2 MAC halothane. CONCLUSIONS: Windup was significantly greater under isoflurane than halothane anaesthesia at 1.2 MAC, whereas the initial C-fibre response was suppressed more by isoflurane. These findings suggest that these two anaesthetics have mechanistically distinct effects on neuronal windup and excitability.
Asunto(s)
Anestésicos por Inhalación/farmacología , Halotano/farmacología , Isoflurano/farmacología , Células del Asta Posterior/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Masculino , Nociceptores/efectos de los fármacos , Células del Asta Posterior/fisiología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacosRESUMEN
The method of c-fos immunohistochemistry was used to identify the brain stem distribution of neurons activated following irritant chemical stimulation of the laryngopharyngeal mucosa. In pentobarbital-anesthetized rats, either water (control), nicotine (600 mM, 1 ml) or capsaicin (330 microM, 1 ml) was applied to the pharynx via a cannula placed posterior to the soft palate. Following nicotine and capsaicin, there was a significant increase in fos-like immunoreactivity (FLI) compared with controls in the following areas: nucleus of the solitary tract from the level of the pyramidal decussation caudally to the level of the area postrema rostrally; dorsomedial aspect of trigeminal subnucleus caudalis (Vc); and paratrigeminal islands interspersed in the spinal trigeminal tract. There was significantly more FLI in Vc and paratrigeminal nuclei following capsaicin than following nicotine, while the reverse was true for NTS. In addition, there was a significant increase in FLI in area postrema and the ventrolateral medullary region dorsal to the lateral reticular nucleus following nicotine but not capsaicin. The distributions of FLI in NTS, area postrema, Vc, and paratrigeminal nuclei are consistent with prior anatomical tract-tracing studies and suggest roles for these brain stem regions in mediating sensory and reflex responses to irritant chemical stimulation of the upper respiratory mucosa.