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. In anaesthetized adult rats with intact peripheral nerves, a conditioning orthodromic volley in myelinated afferents produces a prolonged increase in the excitability of the terminals of the afferents which have carried the orthodromic volley and in the terminals of their passive neighbours. This phenomenon, primary afferent depolarization, p.a.d., is shown by the antidromic stimulation of afferents with a micro-electrode in the dorsal horn and by recording the antidromic volley on a cut peripheral nerve.

2. If a peripheral nerve is cut and ligated, the size of the myelinated afferent volley generated by stimulation proximal to the cut and measured on dorsal roots is not affected for 14 days after the cut (Wall & Devor, 1981). Similarly the size of the volleys ascending the cord in axons from cord cells remains unaffected.

3. If a peripheral nerve is cut and tested after 7-14 days, it produces a markedly decreased p.a.d. on itself and on its neighbours.

4. If a nerve is crushed rather than cut, it produces a normal p.a.d. on itself and its neighbours after 7-14 days.

5. In animals treated neonatally with capsaicin, there is a severe loss of unmyelinated afferents. Testing the effect of an orthodromic volley in myelinated afferents on the excitability of myelinated afferent central terminals shows that there is a strongly decreased p.a.d. in these animals.

6. It is concluded that primary afferent depolarization is sensitive to peripheral nerve lesions and that it may be particularly dependent on the integrity of the unmyelinated afferents in spite of the fact that p.a.d. is measured as a phenomenon of myelinated afferents acting on myelinated afferents.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1982.sp014288

The effect of peripheral nerve lesions and of neonatal capsaicin in the rat on primary afferent depolarization

In the first part of this paper, a series of examples are described where substance P content of afferent C fibres and responses which have been attributed to C fibre excitation vary independently. Thirteen sets of data fail to support the proposal that SP is an excitatory transmitter for noxious inputs. In the second part an alternative hypothesis is proposed in which C fibres would have functions in addition to impulse propagation. It is shown that C fibres are involved in establishing and maintaining the connection between afferent fibres and central cells and that transport mechanisms play a role in this connectivity control. Therefore it is proposed that the chemicals in C fibres should be examined for their possible action on regulatory mechanisms as well as for neurotransmitter action.

If substance P fails to fulfil the criteria as a neurotransmitter in somatosensory afferents, what might be its function?

The relationship of perceived pain to afferent nerve impulses

Dichotomizing somatic nerve fibers exist in rats but they are rare

Wall, Patrick D. and Malcolm Lidierth. Five sources of a dorsal root potential: their interactions and origins in the superficial dorsal horn. J. Neurophysiol. 78: 860–871, 1997. The dorsal root po...

Patrick D. Wall

Papers

The effect of peripheral nerve lesions and of neonatal capsaicin in the rat on primary afferent depolarization

If substance P fails to fulfil the criteria as a neurotransmitter in somatosensory afferents, what might be its function?

The relationship of perceived pain to afferent nerve impulses

Dichotomizing somatic nerve fibers exist in rats but they are rare

Five sources of a dorsal root potential : their interactions and origins in the superficial dorsal horn