Primary Afferent Stimulation Differentially Potentiates Excitatory and Inhibitory Inputs to Spinal Lamina II Outer and Inner Neurons

Abstract

Pan, Yu-Zhen and Hui-Lin Pan. Primary afferent stimulation differentially potentiates excitatory and inhibitory inputs to spinal lamina II outer and inner neurons. J Neurophysiol 91: 2413-2421, 2004. First published January 28, 2004 10.1152/jn.01242.2003. Spinal lamina II (substantia gelatinosa) neurons play an important role in processing of nociceptive information from primary afferent nerves. Anatomical studies suggest that neurons in the outer (lamina II o ) and inner (lamina II i ) zone of lamina II receive distinct afferent inputs. The functional significance of this preferential afferent termination in lamina II remains unclear. In this study, we examined the differential synaptic inputs to neurons in lamina II o and II i in response to primary afferent stimulation. Whole cell voltage-clamp recordings were performed on neurons in lamina II o and II i of the rat spinal cord slice under visual guidance. Capsaicin (1 M) significantly increased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in all 27 lamina II o neurons and significantly increased the amplitude of mEPSCs in 12 of 27 lamina II o neurons. However, capsaicin only significantly increased the frequency of mEPSCs in 9 of 22 (40.9%) lamina II i neurons and increased the amplitude of mEPSCs in 6 of these 9 neurons. Furthermore, the peak amplitude of EPSCs, evoked by electrical stimulation of the attached dorsal root, in 40 lamina II o neurons was significantly greater than that [160.5 Ϯ 16.7 vs. 87.0 Ϯ 10.4 (SE) pA] in 37 lamina II i neurons. On the other hand, the peak amplitude of evoked inhibitory postsynaptic currents (IPSCs) in 40 lamina II o neurons was significantly smaller than that (103.1 Ϯ 11.6 vs. 258.4 Ϯ 24.4 pA) in 37 lamina II i neurons. In addition, the peak amplitudes of both EPSCs and IPSCs, evoked by direct stimulation of lamina II, were similar in lamina II o and II i neurons. This study provides new information that stimulation of primary afferents differentially potentiates synaptic inputs to neurons in lamina II o and II i . The quantitative difference in excitatory and inhibitory synaptic inputs to lamina II o and II i neurons may be important for integration of sensory information from primary afferent nerves. I N T R O D U C T I O NLamina II (substantia gelatinosa) of the spinal cord dorsal horn is a critical site for the relay and processing of primary afferent information (Cervero and Iggo 1980; Light and Perl 1979a;Ralston and Ralston 1979;Woolf and Fitzgerald 1983). With a high density of small interneurons and mostly unmyelinated and thinly myelinated primary afferent terminals, lamina II appears to be a heterogenous region both structurally and functionally. Anatomical studies have divided lamina II into two general subdivisions: an outer lamina II (lamina II o ) with small cells and unmyelinated C-fiber terminals and an inner lamina II (lamina II i ) with slightly larger neurons and predominately thinly myelinated A-fiber endings (Light and Perl 1979a,b;Woodbury et al. 2000). Lam...

N-Methyl-d-aspartate Receptor- and Calpain-mediated Proteolytic Cleavage of K+-Cl− Cotransporter-2 Impairs Spinal Chloride Homeostasis in Neuropathic Pain

“…We used L5 and L6 SNL in adult rats, a commonly used neuropathic pain model (30), to determine whether the loss of synaptic inhibition occurs to glycine-mediated input to spinal lamina II neurons, which also receive nociceptive input (4,5,19,31). We confirmed the presence of mechanical hyperalgesia and tactile allodynia in the hind paw of rats 2 weeks after SNL.…”

“…Recordings-Lumbar spinal cord slices at the L5-L6 level were prepared from adult rats as we described previously (18,19). We removed the lumbar spinal cord through laminectomy during isoflurane-induced anesthesia.…”

“…We sliced the spinal cord (400 m) using vibratome and continually superfused the slices with artificial cerebrospinal fluid containing 117.0 mM NaCl, 3.6 mM KCl, 1.2 mM MgCl 2 , 2.5 mM CaCl 2 , 1.2 mM NaH 2 PO 4 , 11.0 mM glucose, and 25.0 mM NaHCO 3 (bubbled with 95% O 2 , 5% CO 2 ). Because lamina II outer neurons preferentially receive nociceptive afferent input (5,19,20), only neurons in the lamina II outer zone of the spinal cord were recorded. We obtained all perforated voltage-clamp recordings at 34°C using glass pipettes filled with a solution containing 140 mM CsCl, 5 mM EGTA, 10 mM HEPES, pH 7.4, and 50 g ml Ϫ1 gramicidin D (21).…”

“…EPSPs were evoked by electrical stimulation (0.2 ms, 0.6 mA, and 0.1 Hz) through a bipolar stimulating electrode placed on the dorsal root. Data acquisition and analysis of postsynaptic currents and potentials were done as described previously (18,19).…”

Removing TRPV1-expressing primary afferent neurons potentiates the spinal analgesic effect of δ-opioid agonists on mechano-nociception

“…In the inflammatory pain model, more δ-opioid receptors can be recruited to the cell membrane of spinal dorsal horn neurons (Cahill et al, 2003). RTX treatment could cause extensive glutamate release from the primary afferent terminals to the dorsal horn neurons through TRPV1 stimulation (Pan and Pan, 2004). This increased nociceptive input may promote the cell surface expression of δ-opioid receptors on the postsynaptic neurons in the spinal dorsal horn in RTX-treated rats.…”