https://science.sciencemag.org/content/sci/150/3699/971.full.pdf

Pain mechanisms: a new theory.

The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat

Well-being : the foundations of hedonic psychology

A peripheral mononeuropathy was produced in adult rats by placing loosely constrictive ligatures around the common sciatic nerve. The postoperative behavior of these rats indicated that hyperalgesia, allodynia and, possibly, spontaneous pain (or dysesthesia) were produced. Hyperalgesic responses to noxious radiant heat were evident on the second postoperative day and lasted for over 2 months. Hyperalgesic responses to chemogenic pain were also present. The presence of allodynia was inferred from the nocifensive responses evoked by standing on an innocuous, chilled metal floor or by innocuous mechanical stimulation, and by the rats' persistence in holding the hind paw in a guarded position. The presence of spontaneous pain was suggested by a suppression of appetite and by the frequent occurrence of apparently spontaneous nocifensive responses. The affected hind paw was abnormally warm or cool in about one-third of the rats. About one-half of the rats developed grossly overgrown claws on the affected side. Experiments with this animal model may advance our understanding of the neural mechanisms of neuropathic pain disorders in humans.

A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.

As humans, we perceive feelings from our bodies that relate our state of well-being, our energy and stress levels, our mood and disposition. How do we have these feelings? What neural processes do they represent? Recent functional anatomical work has detailed an afferent neural system in primates and in humans that represents all aspects of the physiological condition of the physical body. This system constitutes a representation of 'the material me', and might provide a foundation for subjective feelings, emotion and self-awareness.

How do you feel? Interoception: the sense of the physiological condition of the body.

1. Lamina I cells were recorded in the lumbar dorsal horn of decerebrate rats. Their projecting axons were mainly located in the contralateral dorsolateral funiculus (DLF) in the upper cervical cord. 2. The effect on these cells of short and long trains of stimuli applied to the upper cervical DLF was examined by measuring the ongoing activity of the cells, their response to peripheral stimuli, and the size of their receptive fields. 3. The presence of tonic descending influences from brain stem to spinal cord was investigated by measuring the properties of the lamina I cells before and during block of descending impulses. 4. The results of DLF stimulation and of cord block show that substantial and prolonged excitation affected many cells, whereas some were inhibited for shorter periods of time. 5. The experiments were repeated with stimulation of the DLF caudal to chronic section to eliminate descending fibers. The results suggest that the changes of excitability in intact animals were partly produced by stimulation of descending fibers and partly by the invasion of collaterals activated by the antidromic stimulation of the axons projecting from the lamina I cells. 6. Although long trains of DLF stimuli generally excited lamina I cells, only inhibitions were seen in the deep dorsal horn. Moreover, stimulation rostral to an acute unilateral DLF lesion was without effect on lamina I cells but inhibited deep cells. 7. It is proposed that the lamina I cells might activate brain stem circuits, which in turn influence deep dorsal horn cells.

Descending excitation and inhibition of spinal cord lamina I projection neurons

The aim of these experiments was to sample the properties of lamina I neurones with long ascending projections. Recordings have been made from 136 units at the LA/5 level, with ascending axons reaching C2. More than 80% of the units projected via the contralateral dorsolateral white matter and only 10% via the contralateral ventral quadrant. None projected via the dorsal columns. Receptive fields were typically 1–2 cm2 and although a substantial number of units responded to a limited range of intense stim-uli, a greater number of units were fired by both low- and high-threshold stimulation. In contrast to cells of deeper laminae, the majority of units were excited following activation of descending pathways in the dorsolateral funiculus.



The functional role of these units is not obvious, but the location of the ascending projection and the influence of descending pathways does not support the notion that the output of lamina 1 constitutes a simple “pain pathway”.

A system of rat spinal cord lamina 1 cells projecting through the contralateral dorsolateral funiculus.

(1) Systemic capsaicin treatment of neonatal and adult rats is known to affect unmyelinated afferents. However, the systemic route of administration presents several disadvantages and in order to overcome these a method was explored where a single nerve in adult rats was locally treated. (2) Sciatic nerves were exposed and a 10 mm length was soaked for 15 min in 1.5% capsaicin in vehicle or in the vehicle alone (10% Tween 80, 10% ethyl alcohol in saline). (3) Both the capsaicin solution and the vehicle caused acute block of the C compound action potential while in contact with the nerve. Removal of the solutions, however, resulted in substantial recovery of C fibre conduction. The A fibre volley was totally unaffected. (4) 13-21 days after treatment, the size of the myelinated and unmyelinated volleys evoked by maximal stimulation of the capsaicin treated nerve were unchanged but there was a 20% decrease of conduction velocity in the C fibres. (5) The ability of the maximal C volley from the treated nerve to excite cells in the spinal cord was substantially decreased (by 50%) 13-21 days after local capsaicin.

Patrick D. Wall

Papers

Descending excitation and inhibition of spinal cord lamina I projection neurons

A system of rat spinal cord lamina 1 cells projecting through the contralateral dorsolateral funiculus.

Effects of capsaicin applied locally to adult peripheral nerve. I. Physiology of peripheral nerve and spinal cord

The response of rat spinal cord cells to unmyelinated afferents after peripheral nerve section and after changes in substance P levels.

Myelinated afferent fiber types that become spontaneously active and mechanosensitive following nerve transection in the rat.