Scratching the skin, while instantly relieving itch, often aggravates itch over time due to skin injury. To relieve itch, without damaging the skin, a new technique termed cutaneous field stimulation (CFS) was developed and tested on 21 subjects. CFS uses a flexible plate with needle-like electrodes (n = 16) to electrically stimulate nerve fibres in the superficial skin. The electrodes were stimulated consecutively (4 Hz per electrode, pulse duration 1 ms, intensity 0.4-0.8 mA, 25 min). CFS resulted in a pricking and burning sensation that usually faded rather quickly. The burning sensation was still present during a selective block of impulse conduction in myelinated fibres indicating that nociceptive C-fibres are activated by CFS. Furthermore, a flare reaction developed around the CFS electrodes indicating activation of axon reflexes in nociceptive C-fibres. Itch, elicited by transdermal iontophoresis of histamine, was abolished within the skin area pre-treated with CFS, and was reduced to 14% of control 10 cm distally. Contralateral effects were small or non-existent. After 4 h, itch was reduced ipsilaterally to 32% of control. In comparison, 2 h after transcutaneous electrical nerve stimulation (TENS; 10-20 mA, 100 Hz, 25 min) ipsilateral itch was reduced to 56% of control. In conclusion, CFS offers a powerful new method for combating itch. It is suggested that CFS acts through endogenous central inhibitory mechanisms that are normally activated by scratching the skin.
The nociceptive spinal reflex system performs highly precise sensorimotor transformations that require functionally specified synaptic strengths. The specification is gradually attained during early development and appears to be learning dependent. Here we determine the time course of this specification for heat-nociceptive tail withdrawal reflexes and analyze which types of primary afferents are important for the learning by applying various forms of noninvasive sensory deprivations. The percentage of erroneous heat-nociceptive tail withdrawal reflexes (i.e., movements directed toward the stimulation) decreased gradually from 64.1 +/- 2.5% (mean +/- SEM) to <10% during postnatal days 10-21. This improvement was completely blocked by anesthetizing the tail during the adaptation period, confirming that an experience-dependent mechanism is involved in the specification of synaptic strengths. However, the results show that the adaptation occurs to a significant extent despite local analgesia and protection of the tail from noxious input, provided that tactile sensitivity is preserved. Therefore, it appears that a nociceptive input is not necessary for the adaptation, and that input from tactile receptors can be used to guide the nociceptive synaptic organization during development. Sensory deprivation in the adult rat failed to affect the heat-nociceptive withdrawal reflex system, indicating that the adaptation has a "critical period" during early development. These findings provide a key to the puzzle of how pain-related systems can be functionally adapted through experience despite the rare occurrence of noxious input during early life.
The projection of primary afferents onto spinal interneurons constitutes the first step in sensorimotor transformations performed by spinal reflex systems. Despite extensive studies on spinal somatotopy, uncertainties remain concerning the extent and significance of representational overlap and relation to spinal reflex circuits. To address these issues, the cutaneous projection from the hindpaw and its relation to the topography of lamina V neurons encoding withdrawal reflex strength ("reflex encoders") was studied in rats. Thin and coarse primary afferent terminations in laminas II and III-IV, respectively, were mapped by wheat germ agglutinin-horseradish peroxidase and choleragenoid tracing. The functional weights of these projections were characterized by mapping nociceptive and tactile field potentials and compared with the topography of reflex encoders. Both anatomical and physiological data indicate that thin and coarse skin afferent input is spatially congruent in the horizontal plane. The representation of the hindpaw in the spinal cord was found to be intricate, with a high degree of convergence between the projections from different skin sites. "Somatotopic disruptions" such as the representation of central pads medial to that of the digits were common. The weight distribution of the cutaneous convergence patterns in laminas III-IV was similar to that of lamina V reflex encoders. This suggests that the cutaneous convergence and features such as somatotopic disruptions have specific relations to the sensorimotor transformations performed by reflex interneurons in the deep dorsal horn. Hence, the spinal somatotopic map may be better understood in light of the topography of such reflex systems.
The withdrawal reflex system of higher vertebrates has been extensively used as a model for spinal sensorimotor integration, nociceptive processing and plasticity. In the rat, the nociceptive withdrawal reflex system appears to have a modular organization. Each reflex module controls a single muscle or a few synergistic muscles, and its cutaneous receptive field corresponds to the skin area withdrawn upon contraction of the effector muscle(s) when the limb is in the standing position. This organization principle is at odds with the 'flexion reflex' concept postulated from cat studies. To assess the generality of the modular organization principle we have therefore re-examined the cutaneous input to the withdrawal reflex system of the cat. The cutaneous receptive fields of hindlimb and forelimb muscles were mapped using calibrated noxious pinch stimulation and electromyographic recording technique in barbiturate anaesthetized animals. The investigated muscles had specific cutaneous receptive fields that appeared to correspond to the area of the skin withdrawn upon contraction of the muscle when the limb is in the standing position. The spatial organization of receptive fields in the cat was similar to that in the rat. However, differences in gain properties of reflexes to some anatomically equivalent muscles in the two species were observed, possibly reflecting adaptations to the biomechanics characteristic of the digitigrade and plantigrade stance in cats and rats, respectively. Implications of the findings for the generality of the modular organization of the withdrawal reflex system and for its adaptive properties are discussed.
Recent studies indicate a modular organization of the nociceptive withdrawal reflex system. Each module has a characteristic receptive field, closely matching the withdrawal movement caused by its effector muscle. In the rat, the strength of the sensory input to each module is tuned during the first postnatal weeks, i.e., erroneous spinal connections are depressed, and adequate connections are strengthened. To clarify if this tuning is dependent on supraspinal structures, the effect of a complete neonatal spinal cord transection on the postnatal tuning of withdrawal reflexes was studied. The nociceptive receptive fields of single hindlimb muscles and compound withdrawal reflexes were examined in decerebrate unanesthetized and awake rats, respectively. Noxious thermal CO(2) laser stimulation was used to evoke reflex responses. Neonatal spinal cord transection resulted in a disrupted reflex organization in the adult rat, resembling that previously found in neonatal rats. The receptive fields of single hindlimb muscles exhibited abnormal distribution of sensitivity not matching the withdrawal action of the effector muscles. Likewise, the composite nocifensive movements, as documented in the awake rat, often resulted in erroneous movements toward the stimulus. It is concluded that withdrawal reflexes do not become functionally adapted in rats spinalized at birth. These findings suggest a critical role for supraspinal systems in the postnatal tuning of spinal nociceptive systems.
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