Cutaneus Trunci Muscle Reflex Research Articles

Central Plasticity of Cutaneous Afferents Is Associated with Nociceptive Hyperreflexia after Spinal Cord Injury in Rats.

Electrical stimulations of dorsal cutaneous nerves (DCNs) at each lumbothoracic spinal level produce the bilateral cutaneus trunci muscle (CTM) reflex responses which consist of two temporal components: an early and late responses purportedly mediated by Aδ and C fibers, respectively. We have previously reported central projections of DCN A and C fibers and demonstrated that different projection patterns of those afferent types contributed to the somatotopic organization of CTM reflex responses. Unilateral hemisection spinal cord injury (SCI) was made at T10 spinal segments to investigate the plasticity of early and late CTM responses 6 weeks after injury. Both early and late responses were drastically increased in response to both ipsi- and contralateral DCN stimulations both above (T6 and T8) and below (T12 and L1) the levels of injury demonstrating that nociceptive hyperreflexia developed at 6 weeks following hemisection SCI. We also found that DCN A and C fibers centrally sprouted, expanded their projection areas, and increased synaptic terminations in both T7 and T13, which correlated with the size of hemisection injury. These data demonstrate that central sprouting of cutaneous afferents away from the site of injury is closely associated with enhanced responses of intraspinal signal processing potentially contributing to nociceptive hyperreflexia following SCI.

Temporal and spatial dynamics of spinal sensorimotor processing in an intersegmental cutaneous nociceptive reflex.

The cutaneus trunci muscle (CTM) reflex produces a skin "shrug" in response to pinch on a rat's back through a three-part neural circuit: 1) A-fiber and C-fiber afferents in segmental dorsal cutaneous nerves (DCNs) from lumbar to cervical levels, 2) ascending propriospinal interneurons, and 3) the CTM motoneuron pool located at the cervicothoracic junction. We recorded neurograms from a CTM nerve branch in response to electrical stimulation. The pulse trains were delivered at multiple DCNs (T6-L1), on both sides of the midline, at two stimulus strengths (0.5 or 5 mA, to activate Aδ fibers or Aδ and C fibers, respectively) and four stimulation frequencies (1, 2, 5, or 10 Hz) for 20 s. We quantified both the temporal dynamics (i.e., latency, sensitization, habituation, and frequency dependence) and the spatial dynamics (spinal level) of the reflex. The evoked responses were time-windowed into Early, Mid, Late, and Ongoing phases, of which the Mid phase, between the Early (Aδ fiber mediated) and Late (C fiber mediated) phases, has not been previously identified. All phases of the response varied with stimulus strength, frequency, history, and DCN level/side stimulated. In addition, we observed nociceptive characteristics like C fiber-mediated sensitization (wind-up) and habituation. Finally, the range of latencies in the ipsilateral responses were not very large rostrocaudally, suggesting a myelinated neural path within the ipsilateral spinal cord for at least the A fiber-mediated Early-phase response. Overall, these results demonstrate that the CTM reflex shares the temporal dynamics in other nociceptive reflexes and exhibits spatial (segmental and lateral) dynamics not seen in those reflexes.NEW & NOTEWORTHY We have physiologically studied an intersegmental reflex exploring detailed temporal, stimulus strength-based, stimulation history-dependent, lateral and segmental quantification of the reflex responses to cutaneous nociceptive stimulations. We found several physiological features in this reflex pathway, e.g., wind-up, latency changes, and somatotopic differences. These physiological observations allow us to understand how the anatomy of this reflex may be organized. We have also identified a new phase of this reflex, termed the "mid" response.

Effects of methylprednisolone and 4-chloro-3-hydroxyanthranilic acid in experimental spinal cord injury in the guinea pig appear to be mediated by different and potentially complementary mechanisms.

Blinded, placebo-controlled, parallel treatment group studies of the effects of methylprednisolone (MP) or 4-chloro-3-hydroxyanthranilate (4-Cl-3-HAA) on behavioral outcome and quinolinic acid tissue levels from experimental thoracic spinal cord injury in adult guinea pigs. To compare the effects of treatment with high-dose MP, a corticosteroid, and 4-Cl-3-HAA, a compound that inhibits synthesis of the neurotoxin quinolinic acid (QUIN) by activated macrophages. To explore the effect of different times of treatment using these two approaches to ameliorating secondary tissue damage. Laboratory animal studies at the University of North Carolina, Chapel Hill, NC, USA. Standardized spinal cord injuries were produced in anesthetized guinea pigs, using lateral compression of the spinal cord. Behavioral impairment and recovery were measured by placing and toe-spread responses (motor function), cutaneus trunci muscle reflex receptive field areas and somatosensory-evoked potentials (sensory function). Tissue quinolinic acid levels were measured by gas chromatograph/mass spectrometry. The current experiments showed a reduction in delayed loss of motor and sensory function in the guinea pig with MP (150 mg kg(-1), intraperitoneally in split doses between 0.5 and 6 h), but no significant reduction in tissue QUIN. Improved sensory function was seen with a single dose of 60 mg kg(-1) MP intraperitoneally at 5 h after injury, but not at 10 h after injury. A single dose of 4-Cl-3-HAA at 5 h in the guinea pig did not produce the sensory and motor improvements seen in previous studies with 12 days of dosing, beginning at 5 h. These studies, together with earlier findings, indicate that both drugs can attenuate secondary pathologic damage after SCI, but through separate mechanisms. These are most likely an acute reduction by MP of oxidative processes and reduction by 4-Cl-3-HAA of QUIN synthesis.

Localization of the cutaneus trunci muscle reflex in horses

To determine the magnitude and location of skin movement attributable to the cutaneus trunci muscle reflex in response to localized stimulation of the skin of the dorsolateral aspect of the thoracic wall in horses. 8 horses. A grid of 56 reflective markers was applied to the lateral aspect of the body wall of each horse; markers were placed at 10-cm intervals in 7 rows and 8 columns. A motion analysis system with 10 infrared cameras was used to track movements of the markers in response to tactile stimulation of the dorsolateral aspect of the thoracic wall at the levels of T6, T11, and T16. Marker movement data determined after skin stimulation were used to create a skin deformation gradient tensor field, which was analyzed with custom software. The sites of maximal skin deformation were located close to the stimulation sites; the centers of the twitch responses were located a mean distance of 7.7 to 12.8 cm ventral and between 6.6 cm cranial and 3.1 cm caudal to the stimulation sites. Findings of this study may have implications for assessment of nerve conduction velocities of the cutaneus trunci muscle reflex and may enhance understanding of the responses of horses to placement of tack or other equipment on skin over the cutaneus trunci muscles.

4-Chloro-3-Hydroxyanthranilate Reduces Local Quinolinic Acid Synthesis, Improves Functional Recovery, and Preserves White Matter after Spinal Cord Injury

Inflammatory processes within the central nervous system (CNS) contribute significantly to the pathogenesis of a broad range of neurologic diseases, including spinal cord injury (SCI). One mechanism by which immune activation causes neurologic symptoms and tissue injury is via the production of neurotoxins by activated macrophages and microglia. In the present study, the role of the endogenous tryptophan metabolite and neurotoxin quinolinic acid (QUIN) in secondary pathology following traumatic SCI was investigated. Adult Hartley guinea pigs were injured by lateral compression of the spinal cord at the 12th thoracic segment (T12). QUIN had accumulated at the site of injury on day 12 post-injury in proportion to the severity of functional neurologic deficits (as assessed by the cutaneus trunci muscle reflex and motor function score at 5 h post-injury). Systemic administration of the 3-hydroxyanthranilate-3,4-dioxygenase (3-HAD) inhibitor, 4-chloro-3-hydroxyanthranilate (4Cl-3HAA; approximately 100 mg/kg every 12 h, beginning 5 h after injury) attenuated local QUIN production and reduced QUIN accumulation at the site of injury by approximately 50% at day 12, without enhanced accumulations of the neuroprotective metabolite kynurenic acid (KYNA). The severity of secondary functional deficits was also reduced by 4Cl-3HAA. In toluidine blue-stained spinal cord sections, the area of surviving intact white matter at the injury site was increased by approximately 100% in the 4Cl-3HAA-treated group. Sparing of both axons and myelin contributed to this increase. These results support the conclusion that QUIN accumulations at the site of injury contribute to secondary functional deficits and tissue damage following SCI.

Reduction of Postincisional Allodynia by Subcutaneous Bupivacaine

An incision of hairy skin of the rat's back provides a new model for postincisional pain to determine the importance of cutaneous anesthesia. Male Sprague-Dawley rats were anesthetized with sevoflurane and given a 0.6-ml subcutaneous injection of bupivacaine (0.25%) under the incision site or the medial lumbar dorsum or at the nuchal midline, 30 min before a 1.0-cm skin incision. Mechanical stimuli (von Frey hairs, 18-250 mN) were applied to measure nociception, indicated by twitching of local subcutaneous muscles, the cutaneus trunci muscle reflex. A graded response score, averaging the twitches weighted by their vigor, or a population response score, measuring the fraction of rats that showed any response, was assessed for 3 days before and over 7 days after incision. von Frey hairs were applied 0.5 cm from the incision to test primary hyperalgesia and 2.0 cm contralateral to the incision for secondary hyperalgesia. Incision induced responses to stimuli that had no effect on intact skin (allodynia) and also enhanced responses to forces that normally gave less than the full reflex (hyperalgesia). Hyperalgesia was present 30 min after surgery, peaked at 3-6 h, and persisted through the week; allodynia had a similar onset but was briefer. Both changes were transiently reversed by subcutaneous morphine (2.5 mg/kg intraperitoneal). Subcutaneous bupivacaine (0.25%), injected preoperatively at the incision site and anesthetizing skin for 2-3 h, suppressed primary allodynia for 1 week but had no effect on hyperalgesia. Secondary allodynia was obliterated, and secondary hyperalgesia attenuated by this treatment. Bupivacaine injected subcutaneously at the nuchal midline before surgery was also effective in abbreviating primary and secondary allodynia, with no signs of sedation, ataxia, or preconvulsive behavior. Incision of rat hairy skin changes pain responses, similar to pain in humans. Preincisional subcutaneous bupivacaine selectively suppresses and shortens allodynia for times far outlasting its local anesthesia, an effect largely from systemic actions.

Delayed application of direct current electric fields in experimental spinal cord injuries.

The cutaneus trunci muscle (CTM) reflex of guinea pigs depends on an ascending afferent pathway within the ventrolateral funiculus of the thoracic spinal cord. The expression of this reflex is a phasic contraction of back skin in response to tactile stimulation, which is permanently eliminated by transection of the ventrolateral funiculus. It was shown previously that when a polarized (rostrally negative), weak (300-400 μV/mm) DC electric field is placed across a lateral hemisection of the spinal cord in adult guinea pigs at the time of injury, approximately 13% recover the reflex, while sham-treated animals remain unchanged. In this study, a similar approach was used, except that three months were allowed to pass between the time of hemisection and experimental treatment. No recovery of the CTM reflex was observed in 13 animals with rostrally negative fields, 8 of which were followed for at least 9 months, 5 for 3 months; or in 11 animals with caudally negative applied fields, 8 of which were followed for 9 months and 3 for 3 months.

The Effects of 4-Aminopyridine on Neurological Deficits in Chronic Cases of Traumatic Spinal Cord Injury in Dogs: A Phase I Clinical Trial

A Phase I trial of 4-aminopyridine (4-AP) was carried out in 39 dogs referred to the veterinary teaching hospital with naturally occurring traumatic paraplegia or paraparesis. The rationale for the study was provided by the observation that 4-AP restores conduction in demyelinated nerve fibers in experimental spinal cord injury. Most injuries (77%) resulted from degenerative disk disease, occurring at or near the thoracolumbar junction, and producing chronic, complete paraplegia. Neurological examination of each dog was recorded on videotape before and at intervals after administration of 4-AP. The drug was administered systemically in total doses between 0.5 and 1 mg/kg body weight. Three areas of neurological status changed significantly at 15-45 minutes following administration of 4-AP: (a) striking improvements in hindlimb placing occurred in 18 animals; (b) increased awareness of painful stimuli to the hindlimb in 10 animals; (c) partial recovery of the cutaneus trunci muscle reflex of the back skin in 9 animals. These effects reversed within a few hours of administration. Other animals (36%) showed no change in neurological signs except a slight enhancement of hindlimb reflex tone. Significant side effects were seen in 6 dogs receiving higher intravenous doses, with elevation of body temperature and apparent anxiety, leading to mild seizures in 3 of the animals. These seizures were controlled with diazepam. The results indicate that conduction block may contribute significantly to functional deficits in closed-cord injuries and that potassium channel blockade may prove to be a valid, if limited approach to therapeutic intervention in chronic paraplegia and paraparesis.

Cutaneus trunci muscle reflex of the guinea pig

The cutaneus trunci muscle reflex in guinea pigs was studied with a combination of video analysis, electromyography, lesioning, and light microscopy. The muscle forms a bilateral, subdermal sheet over much of the trunk. Local contractions of the dorsal part of the muscle are produced in response to brief tactile or electrical stimulation of the skin and consist of a twitch centered 1-2 cm rostral of the stimulus site. The reflex receptive field covers most of the thoracic and lumbar dorsal surface. The sensory information is carried via segmental dorsal cutaneous nerves. Receptive fields of adjacent nerves overlap and form rectangular areas perpendicular to the midline, at thoracic levels. Motor innervation projects through the lateral thoracic nerves of the brachial plexus. The motoneurons are located near the cervical thoracic junction (C7-T1). Lesions of the lower thoracic cord indicate that ascending sensory information is carried to the motor nuclei via the ventral half of the lateral funiculus. This pathway conveys information primarily from ipsilateral skin. There is a weaker input from contralateral skin, crossing at segmental levels. Electromyographic responses to brief electrical stimulation of lower thoracic skin occur usually as 10-12 msec bursts at latencies of 10-20 msec, and do not readily habituate or fatigue at stimulus frequencies below 10 Hz. The reflex persists under light pentobarbital anesthesia. This combination of characteristics makes the reflex useful for a variety of physiological and pathophysiological studies.

Functional recovery after spinal cord hemisection in guinea pigs: The effects of applied electric fields

Right lateral hemisection of the lower thoracic spinal cord was performed in 216 adult guinea pigs. Animals that proved suitable for the study were divided into one control and two experimental groups. Experimental animals were implanted with intraperitoneal stimulators delivering regulated current of 35 or 50 microA through electrodes placed 1 cm rostral and caudal of the hemisection. The cathode was cranial to the lesion in one group (n = 67) and caudal in the other (n = 33). Control animals (n = 62) were implanted with sham stimulators and electrodes delivering no current. The functional status of the animals was measured by tactile stimulation of the back skin to elicit the cutaneus trunci muscle reflex, and by the vestibulospinal free-fall response. The cutaneous response ipsilateral and caudal to the lesion was lost following hemisection and did not recover in any of the control animals or in animals with cathode caudal to the lesion. Recovery of the response was found in 9 of 67 animals in the cathode rostral group, between 56 and 139 days after injury. Toe spreading recovered spontaneously in 80-90% of animals in all groups. Of the possible mechanisms of skin reflex recovery, most current evidence points to regrowth of ascending nerve fibers in the lateral funiculus of the spinal cord local to the lesion.

Descending pathways to the cutaneous trunci muscle motoneuronal cell group in the cat.

1. The cutaneus trunci muscle (CTM) is a thin broad sheet of skeletal muscle just beneath the skin. It does not contain muscle spindles and receives its afferents from the overlying skin. Contraction of the muscle can easily be triggered by pinching the skin or, in the cat, by gentle displacement of the fur (CTM reflex). The afferent information of this reflex is conveyed via the cutaneous nerves, which are segmentally organized. In the cat, the CTM motoneurons are located in a circumscribed cell group in the ventrolateral part of the ventral horn of the C8 and T1 spinal segments. The CTM motor nucleus corresponds with "nucleus X" of Giovanelli Barilari and Kuypers and with "ventral motor nucleus" of Matsushita and Ueyama. 2. Relatively long ascending propriospinal pathways, originating in the thoracolumbar cord, exist between the cutaneous afferents and the CTM motor nucleus. Such pathways have been described physiologically, as well as anatomically. Our results, based on anterograde autoradiographic experiments with [3H]leucine injections in the C1, C2, C6, and C8 segments, suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do not exist, although these propriospinal projections are very strong to all other motoneuronal cell groups surrounding the CTM motor nucleus. 3. The present results also demonstrate specific supraspinal projections to the CTM motor nucleus originating in 1) the contralateral nucleus retroambiguous (NRA) and 2) the ipsilateral dorsolateral pontine tegmentum. These projections suggest that the CTM motor nucleus is not only involved in spinal reflexes, but also in other functions such as abdominal straining.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrinsic organization of the rat cutaneus trunci motor nucleus.

1. We have investigated how the organization of the cutaneus trunci muscle (CTM) motor nucleus might correspond to the pattern of its physiological activation (see accompanying report, 61) by using HRP to label retrogradely the motoneurons supplying different anatomically and physiologically defined muscle compartments. The CTM motoneuron pool was found to be comprised of a tightly packed column of ventrolaterally located cells extending from caudal C6 to rostral T1 and to contain 1,183 cells per side; this unusually large number of motoneurons is consistent with the precisely localized reflex behavior exhibited by the muscle. 2. Each of three major motor nerves that functionally divide the CTM into three major longitudinal muscle fields (dorsal, lateral, ventral) was found to derive from a distinct subcolumn of motoneurons, which extends for the full rostrocaudal length of the parent CTM motor nucleus, such that the dorsal motor nerves derive from a medially located subcolumn, the lateral motor nerves from a centrally located subcolumn, and the ventral motor nerves from a subcolumn of motoneurons that sits most laterally in the CTM motor nucleus. 3. Localized injections of HRP into different rostrocaudal regions of the muscle revealed a further subdivision of the CTM motor nucleus: motoneurons located rostrally in the motoneuron pool supplied the rostral regions of the muscle, whereas more caudally located motoneurons in the pool supplied progressively more caudal sites in the muscle. 4. These results reveal the existence of both a mediolateral and a rostrocaudal subdivision of the motor nucleus; thus this intrinsic spatial organization of motoneurons relates the CTM motor nucleus topographically to the body coordinates of its target, the muscle. The possible relation of these findings to the expression of local sign in the CTM reflex, and how the underlying circuitry could develop appropriately, is discussed.

Nociceptive cutaneous stimuli evoke localized contractions in a skeletal muscle.

1. The cutaneus trunci muscle (CTM) is a thin broad sheet of skeletal muscle that originates bilaterally on the humerus and inserts beneath the dermis of back and flank skin. A nociceptive stimulus applied to the skin elicits a localized reflex contraction in that region of the CTM underlying the site of sensory stimulation. While this "local sign" character of the CTM reflex corresponds to the segmental distribution of the afferent nerves (the dorsal cutaneous nerves, or DCNs) that enter the spinal cord in the lower thoracic and the lumbar levels, the motor output originates entirely from a circumscribed region of the cervical spinal cord. 2. Electrophysiological analysis of EMG activity in the muscle reflexly evoked by direct electrical stimulation of individual DCNs revealed a distinct topographic relationship, in that the shortest latency response of EMG activity in the muscle was consistently located approximately 1.0 cm rostral to the dermatome of the stimulated DCN. 3. Histochemical studies of the CTM show that individual muscle fibers run rostrocaudally, are focally innervated, and in adult rats, are approximately 3.0 cm in length. The major motor nerves exit from the brachial plexus, and functionally they divide the muscle into longitudinal (rostrocaudal) territories, which thus lie orthogonal to the dermatomal pattern of sensory innervation. The localized reflex responses to focal sensory stimuli indicate that the major longitudinal muscle fields contain many "reflex compartments." 4. The compartmentalized nature of the reflex response in the CTM suggests that nociceptive input from any one sensory dermatome has a preferred access to that fraction of the motoneuron pool that supplies the area of muscle underlying that specific region of skin, i.e., there is a sort of "matching" between groups of primary sensory neurons, interneurons, and motoneurons, which relates to the peripheral location of the stimulated nerve endings and of the muscle fibers that are reflexly activated. Although the partitioning of sensory input to motor nuclei has been shown most clearly for monosynaptic Ia connections, the CTM reflex suggests that sensory partitioning may also be demonstrated in a polysynaptic circuit.

Regionally selective elimination of cutaneous thermal nociception in rats by neonatal capsaicin

We have studied thermal and mechanical nociception in anesthetized adult rats that had received subcutaneous injections of capsaicin as neonates. This treatment appeared not to have impaired mechanonociception in any of the body regions that were examined. In contrast, thermal nociception was present in some locations and absent in others. Its total disappearance from back skin correlated with the loss of C fiber responsiveness in the dorsal cutaneous nerves (DCNs); electrical excitation of these nerves now failed to evoke the delayed component of the cutaneus trunci muscle reflex, although the early reflex response, elicited by excitation of the mechanosensitive A delta axons, was unaffected. Heat nociception was similarly eliminated from the nonpad glabrous skin of the paws. When the stimulus was applied selectively to the pads, however, a normal foot-withdrawal response was evoked. The probable basis of this differential heat responsiveness in the paws was revealed by the use of the Evans Blue technique in untreated animals; antidromic activation of the paw nerves to excite their C fiber population led to dye extravasation in the glabrous skin around the pads but to almost none in the pads themselves, indicating a relative absence in the pads of a nociceptive C fiber innervation. In capsaicin-treated animals, the tail-flick test revealed a significantly reduced responsiveness to noxious heat in the tail. These results may explain some of the anomalies among the reports of the effects of neonatal capsaicin. It appears that in strategically exposed locations exemplified by the paw pads and tail, capsaicin-resistant axons that could be the relatively fast-conducting A delta ones are involved in the signalling of noxious heat.(ABSTRACT TRUNCATED AT 250 WORDS)