NOCICEPTORS AND PAIN TRANSMISSION

NOCICEPTORS AND PAIN TRANSMISSION

There was a faith-healer from Deal,

Who said, 'Although pain isnt real,'

If I sit on a pin

And it punctures my skin,

I dislike what I fancy I feel.

This poem reflects what we hear from persons such as Lawrence of Arabia, that pain is all in the mind. Now we shall discuss the mechanisms by which we feel pain, starting with pain-sensitive endings.

The prevailing theory of pain perception in the 17th century is shown in Figure 1. Descartes had a fairly good notion of "lines" connecting the periphery to the brain as part of this process; he just used a mechanical action instead of nerve conduction to carry the signal.

What is a nociceptor? This term is sometimes used for specialized pain endings, but a more complete definition is a primary afferent nerve with peripheral terminals that can respond differentially to noxious stimuli. Most nociceptor afferents conduct in either the A( or C velocity range (see below). These two types of pain receptors are differentiated by their conduction velocities and the types of stimuli to which they are sensitive.

A( (myelinated) nociceptorsThese conduct at about 20 m/s and respond to noxious mechanical stimulation, especially pinching or pinpricks. A noxious stimulus is defined as one which produces pain; in humans a noxious mechanical stimulus is a pinch of more than about 7 grams, applied to a small area of skin. The receptive field of A( nociceptors in humans is a small cluster of sensitive spots a few mm2in area; it is slightly smaller in primate hairy skin (Georgopoulos, 1974). Some A( nociceptors also respond to heat stimuli.

Kruger et al. (1981) have published a description of a myelinated nociceptor ending in the skin of the cat. By recording from peripheral nerve fibers, they identified receptive areas which only responded to noxious squeezes or pinches delivered to the skin. They then performed biopsies on the sensitive areas and obtained electronmicrographs of the underlying structures, as shown in Figure 2. The endings were innervated by thinly myelinated axons, which could be traced up to the layer of the dermal papillae. At this point the axons (a) lost their sheaths and axons or small branches penetrated into the epidermis (K = keratinocytes). It was considered that peripheral nociceptors of this type were mainly mechanosensitive.

C-polymodal nociceptorsBy far the greatest number of nociceptors in peripheral nerves are unmyelinated C-fibers, which conduct at velocities less than 2 m/s. C-fibers are the most common element in peripheral nerves, and almost all C-fibers are nociceptors (Torebjork, 1974). The major class of nociceptors of this type is C-polymodal nociceptors, or C-PMNs. These respond to mechanical, thermal or chemical stimuli applied to the skin. They have smaller receptive fields than A( nociceptors, and are usually single spots rather than clusters. The discovery of so many C-nociceptors in peripheral nerves made the overall gate theory of pain unnecessary. The properties of A( and C nociceptors are compared in the Table:

NociceptorCond.ReceptiveMyelinThresh.Modality

TypeVelocityField

A(20 m/sCluster-+LowMech.&

few mm2

heat

C