endings contact the midsection of these fibers in an area devoid of contractile machinery. These afferents are stimulated by stretch and signal muscle length and velocity of lengthening. There is also an efferent supply from specialized γ-motoneurons that innervate the contractile ends of the intrafusal fibers. When activated, this causes the ends to contract and in so doing stretches the noncontractile element, including the afferent endings. The function of this efferent system is to regulate the sensitivity of the afferent fibers during active muscle contractions. In the execution of voluntary movements, when activity is supplied to the contractile (extrafusal) fibers of skeletal muscle via the α-motoneurons, there is also modulatory impulse traffic in the γ system – the principle of α-γ coactivation.
Table 2.2 Classification of peripheral nerve afferent and efferent fibers
| Receptor type | Name | Function |
|---|---|---|
| Mechanoreceptors | ||
| Muscle and skeletal | Muscle spindle | Limb position and motion |
| Golgi tendon organ | Muscle tension | |
| Joint receptor | Joint tension and angle | |
| Cutaneous and subcutaneous | Ruffini's ending | Pressure |
| Merkel's disk | Pressure | |
| Meissner's corpuscle | Touch velocity (hairless skin), low frequency vibration (flutter) | |
| Hair receptors | Tactile (hairy skin) | |
| Pacinian corpuscle | Touch acceleration, high-frequency vibration | |
| Thermoreceptors | C bare nerve endings | Warm |
| Aδ myelinated | Cold | |
| Nociceptors | Aδ myelinated | High pressure, thermal and mechanothermal |
| C bare nerve endings | Thermal and mechanothermal, polymodal, tissue damage products |
Fig. 2.6 Two-point discrimination thresholds for different regions of the body, measured as the smallest detectable separation distance between the tips of a calibrated compass. Thresholds vary widely over the body, being at their lowest (2mm) for the finger tips and highest for the forearm, legs, and back (40-50 mm). For selected regions, thresholds are proportional to the diameter of the receptive fields of individual afferents (shown in black). (From [1], with permission)
For the other proprioceptors, joint receptors are located in the connective tissue capsule and they respond to stretch of this tissue to signal joint pressure and angle. Golgi organs are found in the tendons and signal stretch resulting from muscle contraction. In terms of sensation, all these receptor types contribute to the sense of limb position and kinesthesia, along with information from cutaneous mechanoreceptors.
There are separate thermoreceptors for warm or cold stimuli, and like the skin mechanoreceptors they have punctate receptive fields, although they are bare nerve endings rather than encapsulated structures [13]. Warmth is mediated by receptors activated by a range of temperatures between approximately 32 °C and 45 °C, the discharge rate being proportional to temperature. Above 45 °C heat pain, rather than warmth, is perceived, due to the activity of thermal nociceptors, and within this range the discharge of warm receptors actually decreases. Cutaneous cold receptors are activated by temperatures from 1 °C to approximately 20 °C below ambient skin temperature, discharge frequency being roughly proportional to temperature difference. A sensory illusion called paradoxical cold occurs when a 45 °C hot stimulus is selectively applied to a cold fiber receptive field. The stimulus is perceived as cold (rather than warm or painfully hot, which would be the sensation when applied diffusely to the skin), and this coincides with an increased receptor discharge at these high temperatures.
Fig. 2.7 Schematic of the muscle spindle. The main components of the spindle are the intrafusal muscle fibers, sensory afferent endings, and γ-motoneuron efferent fibers. The intrafusal fibers are devoid of contractile apparatus in the region of the afferent endings, although the ends are contractile and are innervated by the γ-motoneurons. The sensory endings are responsive to stretch of the intrafusal fibers. Contraction of the ends of the fibers alters spindle sensitivity. (From [l], with permission)
Nociceptors are also bare nerve endings and respond selectively to stimuli that are sufficiently intense that they could damage tissue, and to chemicals released as a result of tissue damage [14]. Thermal nociceptors respond selectively to extreme heat or cold; mechanical nociceptors are activated by strong mechanical stimulation, most effectively by sharp objects. Chemically sensitive, mechanically insensitive nociceptors respond to a variety of agents including K+, extremes of pH, and neuroactive substances such as histamine, bradykinin, and prostanoids, as well as various irritants. Polymodal nociceptors respond to combinations of mechanical, thermal, and chemical stimulation.
Pain is an unpleasant sensation triggered by tissue damage, real or potential. The high emotive content lends subjectivity to the experience, and simple stimulation of nociceptors does not necessarily lead to pain sensation under all circumstances: there are descending pathways that influence pain transmission. The physiological activation of nociceptors, though, usually gives rise to pricking, burning, aching, and stinging sensations. When the skin is damaged, the initial sensation is conveyed by Aδ fibers. C fibers are more important for the longer-lasting perception that outlives the stimulus. However, pain can also result from neural damage and changes in neural circuitry, and does not necessarily require activation of nociceptors. This is clearly seen in the case of phantom limb pain after surgical limb amputation. Such neuropathic pain following peripheral nerve injury and degeneration/regeneration can be caused by alterations in the balance of inputs to the spinal cord sensory neurons. Thus, large myelinated neurons may regenerate better than C fibers, so that spinal cord neurons that once had predominantly nociceptive input could now be dominated by Aβ touch fibers, although the central connection would remain appropriate for pain transmission. Such a phenomenon may underlie allodynia, where previously innocuous stimuli become severely painful [2,15].
Sensory Input to the Spinal Cord
The cell bodies of sensory neurons are located in the dorsal root ganglia. These bipolar neurons have a relatively long peripheral axon branch, and those in the dorsal column-medial lemniscal pathway also have an extensive central axonal projection. Thus, the cell bodies have a considerable task to supply nutrients and materials to maintain axonal function. This consideration, combined with the potential effects of diabetes on dorsal root ganglion microenvironment, could contribute to a relative vulnerability of sensory neurons, which would affect both peripheral and central projections. Evidence for involvement of central axons is seen in a reduction of spinal cord cross-sectional area, determined by magnetic resonance imaging in diabetic patients with distal symmetrical polyneuropathy [16].
The architecture of the spinal input reflects the segmental organization of embryonic development. As the embryo grows and expands, the developing skin carries its segmentally derived innervation with it. Thus, a single area of skin, a dermatome, is supplied by axons from a single dorsal root ganglion [1,2]. This dermatomal organization is shown in Figure 2.8. However, peripheral nerves themselves contain axons from several spinal roots, and different nerves can contain axons from the same root, so the relationship between peripheral nerve trunk and dermatome is complex.
In addition to a central projection, there are also local connections in the spinal cord for neurons that
