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Biomedical subjects

Edward R Perl

Publications and source records attributed to Edward R Perl.

9 recordsLinked to original sources
PubMed2007

Ideas about pain, a historical view.

The expression 'painful' can be used to describe both an embarrassing moment and a cut on the finger. An explanation for this dichotomy can be found in the convoluted history of ideas about pain. Whether pain is an independent sensation and the product of dedicated neural mechanisms continues to be a topic of debate. This overview concentrates on the issue of specificity together with other notable information regarding pain that has emerged since 1800.

Animals↗
PubMed2005

Molecular and genetic features of a labeled class of spinal substantia gelatinosa neurons in a transgenic mouse.

Genetic incorporation in a mouse of a transgene containing the prion promoter and the green fluorescent protein (GFP) coding sequence labels a set of substantia gelatinosa (SG) neurons (SG-GFP) homogenous in morphology, electrophysiology, and gamma-amino-butyric acid expression. In the present analysis the SG-GFP neurons are established to have protein kinase C-betaII immunoreactivity and to lack evidence for the presence of calbindin D-28k, parvalbumin, and protein kinase C-gamma. These neurons were hyperpolarized by mediators of descending control, norepinephrine and serotonin. Sequential polymerase chain reactions established the insertion of the transgene to be in the receptor protein tyrosine phosphatase kappa (RPTP-kappa) and the laminin receptor 1 (ribosomal protein SA) pseudogene 1 locus. RPTP-kappa expression in both GFP-labeled dorsal root ganglia and SG neurons raises the possibility that homophilic interactions of RPTP-kappa contribute to establishment of connections between specific classes of primary afferent and SG neurons.

Animals↗
PubMed2005

Modular organization of excitatory circuits between neurons of the spinal superficial dorsal horn (laminae I and II).

Neural circuitry of the spinal superficial dorsal horn (SDH) (laminae I and II) and its relationship to pain and other somatosensory phenomena remain poorly understood. To gain information on this issue, synaptic connections between identified SDH neurons were studied in rat spinal cord slices by simultaneous whole-cell recordings from pairs of cells. Both excitatory and inhibitory connections were noted. This report focuses on the observed excitatory linkages. Synaptic excitatory connections between SDH neurons proved highly selective and consistently were unidirectional. Two patterns repeatedly appeared (for neuron classification, see Materials and Methods) (Grudt and Perl, 2002). Lamina II central neurons, with dorsal root (DR) C-fiber input, monosynaptically excited lamina II vertical neurons with DR Adelta input. Lamina II outer vertical neurons with DR Adelta input monosynaptically excited lamina I neurons. Some of the postsynaptic lamina I cells were shown to project rostrally. In contrast to the usual case for connected neurons, in unconnected pairs, primary afferent input to the same type of neuron proved closely similar. Together, these observations indicate that the neural circuitry in the SDH, including its substantia gelatinosa (lamina II), has an explicit organization in which particular combinations of neurons comprise modules arranged to modify and transmit sensory information arriving from Adelta and C primary afferent fibers.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2004

Morphological and physiological features of a set of spinal substantia gelatinosa neurons defined by green fluorescent protein expression.

The spinal substantia gelatinosa (SG) is known to be involved in the manipulation of nociceptive and thermal primary afferent input; however, the interrelationships of its neuronal components are poorly understood. As a step toward expanding understanding, we took a relatively unique approach by concentrating on a set of SG neurons selectively labeled by green fluorescent protein (GFP) in a transgenic mouse. These GFP-expressing SG neurons prove to have homogenous morphological and electrophysiological properties, are systematically spaced in the SG, contain GABA, receive C-fiber primary afferent input, and upregulate c-Fos protein in response to noxious stimuli. Together, the properties established for these GFP-labeled neurons are consistent with a modular SG organization in which afferent activity related to nociception or other C-fiber signaling are subject to integration/modulation by repeating, similar circuits of neurons.

Animals↗
PubMed2003

A specific inhibitory pathway between substantia gelatinosa neurons receiving direct C-fiber input.

The spinal substantia gelatinosa (SG) is a major termination region for unmyelinated (C) primary afferent fibers; however, how the input it receives from these sensory fibers is processed by SG neurons remains primarily a matter of conjecture. To gain insight on connections and functional interactions between intrinsic SG neurons, simultaneous tight-seal, whole-cell recordings were made from pairs of neurons in rat spinal cord slices to examine whether impulses in one cell generated synaptic activity in the other. Most SG neuron pairs sampled lacked synaptic interaction. Those showing a linkage included a recurring pattern consisting of a monosynaptic, bicuculline-sensitive inhibitory connection from an islet cell to a transient central neuron, each of which received direct excitatory input from different afferent C-fibers. This newly defined inhibitory circuit is postulated to represent a SG neural module by which a nociceptive C-fiber input to transient central cells is modified by other C-fiber messages.

Action Potentials↗
PubMed2002

Hypocretin-2 (orexin-B) modulation of superficial dorsal horn activity in rat.

The hypothalamic peptides hypocretin-1 (orexin A) and hypocretin-2 (Hcrt-2; orexin B) are important in modulating behaviours demanding arousal, including sleep and appetite. Fibres containing hypocretin project from the hypothalamus to the superficial dorsal horn (SDH) of the spinal cord (laminae I and II); however, the effects produced by hypocretins on SDH neurones are unknown. To study the action of Hcrt-2 on individual SDH neurones, tight-seal, whole-cell recordings were made with biocytin-filled electrodes from rat lumbar spinal cord slices. In 19 of 63 neurones, Hcrt-2 (30 nM to 1 microM) evoked an inward (excitatory) current accompanied by an increase in baseline noise. The inward current and noise were unaffected by TTX but were blocked by the P(2X) purinergic receptor antagonist suramin (300-500 microM). Hcrt-2 (30 nM to 1 microM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in the majority of neurones. The sIPSC increase was blocked by strychnine (1 microM) and by TTX (1 microM), suggesting that the increased sIPSC frequency was glycine and action potential dependent. Hcrt-2 increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in a few neurones but had no effect on dorsal root-evoked EPSCs in these or in other neurones. Neurones located in outer lamina II, particularly radial and vertical cells, were most likely to respond to Hcrt-2. We conclude that Hcrt-2 has excitatory effects on certain SDH neurones, some of which exert inhibitory influences on other cells of the region, consistent with the perspective that hypocretin has a role in orchestrating reactions related to arousal, including nociception, pain and temperature sense.

Animals↗
PubMed1977

A comparison of four tests for assessing the pain sensitivity of different subjects and test areas.

Four different testing methods were used to estimate the sensitivity of body surfaces to pain-causing stimuli for a group of 24 healthy male subjects. These methods were (a) determination of the heat pain threshold, (b) determination of the pain threshold for pinching of a skin fold, (c) discrimination of a sharp prick from a blunt contact, and (d) estimation of the pain caused by application of an ice-cold cylinder. Three different body regions were tested: the abdomen, the anterior surface of the neck and the lateral surface of the thigh. Of the three body regions, the thigh area required the strongest stimulation for pain in all 4 tests. The neck was the most sensitive for cold pain, and the abdomen had the lowest threshold for heat pain. There was a barely statistically significant tendency for subjects relatively sensitive on one test to be also relatively sensitive on other tests. Correlation coefficients between any two tests on the same subject were always less than 0.6. Possible reasons for the relative lack of agreement among the results of the different pain tests are discussed.

Abdomen↗