Role of Gelatinous Substance of Spinal Cord in Conduction of Pain

Pearson, Anthony A.

doi:10.1001/archneurpsyc.1952.02320220092011

Cited by 67 publications

(27 citation statements)

References 16 publications

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“…For example, the high receptor densities in laminae I and II of the spinal cord may be involved in modulation of painful stimuli, since these areas appear related to processing of nociceptive stimuli (13,14). Also, analgesia is elicited in animals by application of morphine to the region of the periventricular gray matter and medial thalamus, areas enriched in opiate receptors as evidenced by their high grain densities (15,16).…”

Section: Discussionmentioning

confidence: 99%

Opiate receptor: autoradiographic localization in rat brain.

Pert¹,

Kuhar²,

Snyder³

1976

Proc. Natl. Acad. Sci. U.S.A.

486

107

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METHODSThe procedure for the autoradiographic localization of opiate receptors involves injecting a suitable radioactive opiate antagonist, sacrificing the animal at a time when the bulk of the drug is specifically bound to receptors, and processing the tissue in such a way as to prevent diffusion of drug away from its binding site. The suitability of [3H]diprenorphine is due to its very high affinity for the opiate receptor (KD = 1-2 X 10-10 M) and its corresponding slow dissociation rate from the receptor, especially at low temperatures (6). The data presented here (see Results) and in our preliminary study (6) indicate that 1 hr after injection the bulk of the drug in brain was associated with opiate receptors. We processed the tissue by thawmounting thin sections of fresh, frozen, unfixed tissue to emulsion-coated slides to prevent or minimize diffusion of drug from binding sites (7-10). After exposure, the localization of opiate receptors was inferred from the distribution of silver grains, which are indicative of [3H]diprenorphine binding sites. These techniques have also been utilized in our laboratory to localize the cholinergic muscarinic receptor by autoradiographic methods (11).

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Section: Discussionmentioning

confidence: 99%

Opiate receptor: autoradiographic localization in rat brain.

Pert¹,

Kuhar²,

Snyder³

1976

Proc. Natl. Acad. Sci. U.S.A.

486

107

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“…The superficial dorsal horn (SDH) (laminae I and II) receives a heavy synaptic input from such fibers (Réthelyi and Szentágothai, 1969;Light and Perl, 1979a,b). Classical morphological and modern electrophysiological investigations agree that the SDH is comprised of a variety of neurons embedded in a complex neuropil (Earle, 1952;Pearson, 1952;Réthelyi and Szentágothai, 1969;Ramon y Cajal, 1999;Grudt and Perl, 2002); however, the functional organization of this region remains essentially a mystery. It is known that lamina I, the marginal zone, contains neurons contributing to the spinoreticular and spinothalamic projections that are implicated in processing information important for pain and temperature senses (Kuru, 1949;Perl, 1984;Craig and Kniffki, 1985;Craig, 1994;Han et al, 1998;Ikeda et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…The subjacent lamina II includes several types of neurons in two divisions, an outer (II o ) and inner (II i ), distinguished by characteristics of the constituent neurons and features of the primary afferent projection (Rexed, 1952;Woodbury et al, 2000). Neurons of lamina II have been argued to participate principally in local circuitry, to a large extent within the SDH itself (Pearson, 1952;Szentágothai, 1964;Réthelyi and Szentágothai, 1969;Light, 1992).…”

Section: Introductionmentioning

confidence: 99%

Modular Organization of Excitatory Circuits between Neurons of the Spinal Superficial Dorsal Horn (Laminae I and II)

Lü¹,

Perl²

2005

J. Neurosci.

228

268

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“…Because of this, the region was long associated with pain mechanisms (12,14), a postulate that is now supported by direct evidence (15). However, it has recently been established that the substantia gelatinosa is a region of substantial functional diversity in terms of the peripheral stimuli that effectively excite its neurons (16)(17)(18).…”

mentioning

confidence: 95%

“…The spinal substantia gelatinosa, the region containing FRAP, is a termination zone principally for thin primary afferent fibers (11)(12)(13). Because of this, the region was long associated with pain mechanisms (12,14), a postulate that is now supported by direct evidence (15).…”

mentioning

confidence: 99%

Is ATP a central synaptic mediator for certain primary afferent fibers from mammalian skin?

Fyffe¹,

Perl²

1984

Proc. Natl. Acad. Sci. U.S.A.

138

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The possibility that ATP acts as a synaptic mediator at the central terminals of primary afferent fibers was examined by applying it iontophoretically to neurons of the outer layers of the cat spinal cord in vivo, ATP proved to be selectively excitatory for a limited subset of spinal neurons. Those units consistently excited by ATP iontophoresis with very small currents (2-15 nA) responded to gentle mechanical stimulation of the skin and usually evidenced excitatory input from unmyelinated primary afferent fibers. Most units excited by ATP were specifically mechanoreceptive; a few neurons receiving excitatory input from both low-threshold mechanoreceptors and nociceptors also responded to ATP. Selectively nocireceptive neurons were unresponsive. Generally, the mechanoreceptive neurons excited by ATP were located in the deeper substantia gelatinosa or in the immediately adjacent nucleus proprius of the dorsal horn. The results suggest the presence of a purinergic excitatory receptor on central neurons receiving excitatory projection from tactile mechanoreceptors with finediameter afferent fibers and are consistent with the possibility that an ATP-like agent may mediate central synaptic excitation for this set of sense organs.The list of putative neurotransmitters in the mammalian central nervous system has grown substantially in the past decade. ATP has not received much attention in this regard; although it has long been known to be associated with synaptic vesicles and hormone granules containing other potent neurohumoral or synaptic mediators (1-3), its function in these vesicles has not been established. Speculations about its role have included the provision of energy for the accumulation or release of a transmitter and as a factor in ionic balance (4). There is evidence that ATP is, itself, a specific mediator in the autonomic supply to the mammalian gastrointestinal tract (5). Another possibility for ATP in synaptic function has emerged as a result of work by Jessell's group (6) on the fluoride-resistant acid phosphatase (FRAP) found in the spinal substantia gelatinosa of the rat. They found that FRAP acts selectively on 5' nucleotide substrates (6) and that in cultures of mixed spinal dorsal horn neurons from the rat, locally applied ATP excites a subpopulation of neurons (7). These observations led them to revive Holton and Holton's proposal of 1954 (8) that a releasable store of ATP contained in some dorsal root ganglion neurons acts as a central and peripheral mediator. In the past, this idea generated little enthusiasm. In vivo tests in rat and cat found locally applied ATP to have little or no selectivity in activating functionally defined central neurons, and it has been proposed that the excitatory actions of ATP are the result of a nonspecific calcium chelation (9, 10).The spinal substantia gelatinosa, the region containing FRAP, is a termination zone principally for thin primary afferent fibers (11-13). Because of this, the region was long associated with pain mechanisms (12, 14), a postu...

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Role of Gelatinous Substance of Spinal Cord in Conduction of Pain

Cited by 67 publications

References 16 publications

Opiate receptor: autoradiographic localization in rat brain.

Opiate receptor: autoradiographic localization in rat brain.

Modular Organization of Excitatory Circuits between Neurons of the Spinal Superficial Dorsal Horn (Laminae I and II)

Is ATP a central synaptic mediator for certain primary afferent fibers from mammalian skin?

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