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Biomedical subjects

W Jänig

Publications and source records attributed to W Jänig.

At least 19 recordsLinked to original sources

[Clinical findings in patients with chronic complex regional pain syndrome].

PURPOSE: What are the clinical findings in patients with chronic complex regional pain syndrome (CRPS)? METHODS: Bedside examination was performed in 40 patients with CRPS and a mean illness duration of 43 months. To evaluate motor and autonomic disturbances, rating scales were developed and applied. Quantitative sensory testing (QST) was conducted in 24 patients. RESULTS: Clinical examination revealed sensory abnormalities in 93% of patients examined (in 56% limited to the affected limb, in 7% in the upper quadrant of the body, in 30% hemisensory impairment of the ipsilateral body side), and 60% of the patients suffered from mechanical allodynia in the affected limb. Patients with generalized sensory impairment had a significantly longer illness duration, pain intensity and significantly higher frequency of mechanical allodynia/hyperalgesia than patients with sensory deficits limited to the limb affected. In patients with generalized sensory abnormalities, QST revealed significant changes of cold, warm and touch thresholds on the ipsilateral compared to the contralateral body side. Mild/moderate motor abnormalities could be demonstrated in 45% of patients, tremor (50%), impaired joint movements, 45%, and 40% of patients revealed autonomic disturbances. CONCLUSION: In chronic CRPS, among clinical symptoms and signs, pain and sensory impairment play a major role. Mechanical allodynia reveals the highest level of subjective disability among all symptoms. With respect to hemisensory impairment, functional disturbances of central pain processing in the nucleus ventralis posterior of the thalamus are postulated.

Adult↗

Neurophysiological tests and neuroimaging procedures in non-acute headache: guidelines and recommendations.

The use of instrumental examinations in headache patients varies widely. In order to evaluate their usefulness, the most common instrumental procedures were evaluated, on the basis of evidence from the literature, by an EFNS Task Force (TF) on neurophysiological tests and imaging procedures in non-acute headache patients. The conclusions of the TF regarding each technique are expressed in the following guidelines for clinical use. 1 Interictal electroencephalography (EEG) is not routinely indicated in the diagnostic evaluation of headache patients. Interictal EEG is, however, indicated if the clinical history suggests a possible diagnosis of epilepsy (differential diagnosis). Ictal EEG could be useful in certain patients suffering from hemiplegic and basilar migraine. 2 Recording of evoked potentials is not recommended for the diagnosis of headache disorders. 3 There is no evidence to justify the recommendation of autonomic tests for the routine clinical examination of headache patients. 4 Manual palpation of pericranial muscles, with standardized palpation pressure, can be recommended for subdividing patient groups but not for diagnosis. Pressure algometry and electromyography (EMG) cannot be recommended as clinical diagnostic tests. 5 In adult and paediatric patients with migraine, with no recent change in attack pattern, no history of seizures, and no other focal neurological signs or symptoms, the routine use of neuroimaging is not warranted. In patients with atypical headache patterns, a history of seizures and/or focal neurological signs or symptoms, magnetic resonance imaging (MRI) may be indicated. 6 If attacks can be fully accounted for by the standard headache classification [International Headache Society (IHS)], a positron emission tomography (PET) or single-photon emission computerized tomography (SPECT) and scan will generally be of no further diagnostic value. 7 Nuclear medicine examinations of the cerebral circulation and metabolism can be carried out in subgroups of headache patients for diagnosis and evaluation of complications, when patients experience unusually severe attacks, or when the quality or severity of attacks has changed. 8 Transcranial Doppler examination is not helpful in headache diagnosis. Although many of the examinations described are of little or no value in the clinical setting, most of the tools have a vast potential for further exploring the pathophysiology of headaches and the effects of pharmacological treatment.

Diagnosis, Differential↗

Reflexes in sympathetic vasoconstrictor neurones arising from urinary bladder afferents are not amplified early after inflammation in the anaesthetised cat.

Pathophysiological processes in the viscera can lead to pain and hyperalgesia and exaggerated motility-regulating reflexes. This may be due to sensitisation of visceral afferents (peripheral sensitisation), which has repeatedly been shown to occur as a consequence of e.g. inflammation, and/or to sensitisation of dorsal horn neurones (central sensitisation), which is less well documented in the visceral domain. As an indicator of peripheral sensitisation, we previously analysed the responses of sacral spinal afferents after inflammation of the urinary bladder. Here, we studied reflexes in sympathetic vasoconstrictor neurones supplying skeletal muscle and skin elicited by bladder distension stimuli (vesico-sympathetic reflexes) before and after induction of bladder inflammation. Our aim was to test whether these vesico-sympathetic reflexes are amplified after inflammation in a way that would support a major functional role for post-inflammatory central sensitisation processes. Bladder inflammation was induced in anaesthetised cats by instillation of turpentine or mustard oil and vesico-sympathetic reflexes were studied 1 and 2 h after induction of the inflammation. Inflammation enhanced on-going activity in vasoconstrictor neurones supplying skeletal muscle (after 1 h to 187.6+/-36.8%, mean+/-SEM, P<0.01, and after 2 h to 139.1+/-12.9%, P<0.05, of baseline activity) and decreased it in most sympathetic neurones supplying skin (to 91.7+/-12.5%, P>0.05, and to 71.6+/-11.3%, P<0.05, respectively, of baseline activity). Relative to the altered baseline activity vesico-sympathetic reflexes to graded distension of the inflamed bladder were quantitatively unchanged with a tendency to be diminished. Thus, the changes in on-going sympathetic vasoconstrictor activity and the distension-evoked reflexes directly mirrored the afferent input from the inflamed urinary bladder into the spinal cord, i.e. no increase of the gain of these reflexes was observed. These results suggest that in the first 2 h of inflammation, peripheral sensitisation processes play the main role for hyperalgesia and hyperreflexia of the urinary bladder. In contrast, central sensitisation appears to be of little importance during this time period.

Action Potentials↗

Blockade of nociceptive inhibition of plasma extravasation by opioid stimulation of the periaqueductal gray and its interaction with vagus-induced inhibition in the rat.

We have previously shown that stimulation of cutaneous or visceral nociceptors suppresses inflammation measured as bradykinin-induced synovial plasma extravasation in the knee joint of the rat. This suppression occurs through the activation of a spinal as well as a supraspinal reflex pathway leading to activation of the adrenal medullae and probably the release of epinephrine. These nociceptive-neuroendocrine reflex pathways are tonically inhibited by activity in abdominal vagal afferents acting through an inhibitory descending pathway projecting through the dorsolateral funiculus (DLF) ipsilateral to the cutaneous afferent nociceptive input. Here we investigated whether the descending inhibitory pathway acted upon by vagal afferents is also modulated by the periaqueductal gray (PAG), similar to other bulbo-spinal pathways acting on spinal nociceptive transmission. Injection of morphine sulfate (10 nmol) in the ventrolateral PAG significantly inhibited the nociceptive-neuroendocrine reflex pathways, an effect that was significantly less after removal of vagal afferents (i.e. after release from tonic inhibition maintained by vagal afferents). Interruption of the DLF ipsilateral to the nociceptive input removed the inhibitory effect of vagal afferents and partly reduced the inhibition produced by morphine injected in the PAG. From these investigations we conclude that PAG-induced inhibition of the nociceptive-neuroendocrine reflex pathways is mediated through the DLF ipsilateral to the nociceptive input, involving the same descending inhibitory pathway that relays afferent vagal inhibition, and through other spinal and possibly supraspinal pathways.

Adrenal Medulla↗

Neurophysiological analysis of target-related sympathetic pathways--from animal to human: similarities and differences.

The sympathetic nervous system regulates many different target tissues in the somatic and visceral domains of the body in a differentiated manner, indicating that there exist separate sympathetic pathways that are functionally defined by their target cells. Signals generated by central integration and channelled through the preganglionic neurons into the final sympathetic pathways are precisely transmitted through the para- and prevertebral ganglia and at the neuroeffector junctions to the effector cells. Neurophysiological recordings of activity in postganglionic neurons in skin and muscle nerves using microneurography in human subjects and in skin, muscle and visceral nerves, using conventional recording techniques in anaesthetized animals, clearly show that each type of sympathetic neuron exhibits a discharge pattern that is characteristic for its target cells and, therefore, its function. These findings justify labelling the neurons as muscle vasoconstrictor, cutaneous vasoconstrictor, sudomotor, lipomotor, cardiomotor, secretomotor neurons, etc. The discharge patterns monitor aspects of the central organization of the respective sympathetic system in the neuraxis and forebrain. They can be dissected into several distinct reflexes (initiated by peripheral and central afferent inputs) and reactions connected to central signals (related to respiration, circadian and other rhythms, command signals generated in the forebrain, etc). They are functional markers for the sympathetic final pathways. These neurophysiological recordings of the discharge patterns from functionally identified neurons of sympathetic pathways in the human and in animals are the ultimate reference for all experimental investigations that aim to unravel the central organization of the sympathetic systems. The similarities of the results obtained in the in vivo studies in the human and in animals justify concluding that the principles of the central organization of sympathetic systems are similar, if not identical, at least in the neuraxis, in both species. Future progress in the analysis of the central neuronal circuits that are associated with the different final sympathetic pathways will very much depend on whether we are able to align the human models and the animal models. Human models using microneurography have the advantage to work under awake conditions. The activity in the postganglionic neurons can be correlated with various other (afferent, centrally generated) signals, effector responses, perceptions, central changes monitored by imaging methods, etc. However, human models have considerable limitations. Animal models can be divided into in vivo models and various types of reduced in vitro models. Animal models allow using various methodological approaches (e.g., neurophysiological, pharmacological, modern anatomical tracing methods; behavioural animal models; transgenic animals), which cannot be used in the human. Interaction of the research performed in the human and animals will allow to design animal models that are relevant for diseases in which the sympathetic nervous systems is involved and to trace down the underlying pathophysiological mechanisms. The scientific questions to be asked are formulated on the basis of clinical observations resulting in testable hypotheses that are investigated in the in vivo human and animal models. Results obtained in the in vivo models lead to the formulation of hypotheses that are testable in reduced in vivo and particularly in vitro animal models. Microneurographic recordings from sympathetic postganglionic fibres in the human will keep its place in the analysis of the sympathetic nervous system in health and disease although only relatively few laboratories in the world will be able to keep the standards and expertise to use this approach. Experimental investigation of the organization of the sympathetic nervous system in animal models has changed dramatically in the last 15 years. The number of in vitro models and the methodological diversity have increased. In vivo experimentation on larger animals has almost disappeared and has been replaced by experimentation on rats, which became the species for practically all types of studies on the central organization of the sympathetic nervous system.

Action Potentials↗

Relationship between pain and autonomic phenomena in headache and other pain conditions.

Involvement of the (efferent) autonomic nervous system in the generation of pain is ongoing matter of debate. Based on clinical and experimental observations, there are good arguments that the sympathetic nervous system may be involved in pain following trauma, with and without nerve lesion, at an extremity, such as in complex regional pain syndrome type I and II. However, the mechanisms involved are in many cases still unclear. In various types of headache there is no convincing evidence that the sympathetic nervous system is involved in the generation of pain, although these pains may be accompanied by considerable autonomic reactions which are dependent on activity in sympathetic neurons. Migraine and headaches with autonomic symptoms are accompanied by autonomic reactions which are dependent on activity in cranial parasympathetic neurons. Whether parasympathetic neurons innervating cranial blood vessels are involved in activation or sensitization of trigemino-vascular afferents is discussed and needs experimental verification.

Animals↗

[Visceral pain--a neglected phenomenon in pain therapy and research?].

The topic "visceral pain"is hardly covered in basic research and pain therapy. After low back pain, headache and musculosceletal pain is abdominal pain the 4th frequent chronic pain syndrome in the general population with considerable direct and indirect disease related costs.An interdisciplinary multimodal treatment of chronic abdominal pain syndromes is rarely practiced in clinical care.

Gastrointestinal Diseases↗

[Physiology and pathophysiology of visceral pain].

Visceral pain is diffusely localized, referred to deep somatic tissues, skin and viscera, frequently not correlated with an actual trauma, commonly correlated with strong negative affective reactions and accompanied by strong protective autonomic and motor reactions. It is correlated with the excitation of spinal (thoraco-lumbar, sacral) visceral afferents and (with a few exceptions) not with the excitation of vagal afferents. Spinal visceral afferents are polymodal and can be excited by physical and chemical stimuli. All groups of visceral afferents can be sensitized (e.g.by inflammation). Normally silent (mechanically insensitive) visceral afferents are recruited by inflammation. Individual visceral afferent neurons project in laminae I and V of the dorsal horn over several segments, medio-lateral over the entire width of the dorsal horn and to the contralateral side. Their activity is synaptically transmitted, in these and deeper laminae, to viscero-somatic convergent neurons which receive additional afferent synaptic input from skin and deep somatic tissues of the corresponding dermatomes,myotomes and sclerotomes. The mechanism of sensitization of viscerosomatic convergent neurons (central sensitization) during sensitization of spinal visceral afferents is unclear.Viscero-somatic tract neurons project to lower and upper brain stem,hypothalamus and via the thalamus to various cortex areas. Visceral nociception and pain is presumably (together with other visceral sensations and homeostatic regulations of autonomic body functions) primarily represented in the insula in the context of interoception. The insula obtains its main peripheral afferent input from lamina I neurons via the Nucleus ventromedialis posterior of the thalamus. The transmission of visceral impulses in the spinal cord is modulated by the endogenous control systems in the brain stem which are in turn under the control of cortex and limbic system.

Afferent Pathways↗

Spino-bulbo-spinal pathway mediating vagal modulation of nociceptive-neuroendocrine control of inflammation in the rat.

Stimulation of nociceptors by intradermal capsaicin produces depression of bradykinin (BK)-induced synovial plasma extravasation (PE) that is markedly enhanced by subdiaphragmatic vagotomy. This depression is mediated by the adrenal medullae, a propriospinal pathway between the afferent nociceptive input and preganglionic neurones projecting to the adrenal medullae, and a spino-bulbo-spinal pathway. Here we investigated the role of spinal ascending and descending pathways in the interaction between noxious and vagal afferent inputs, leading to inhibition of BK-induced PE mediated by the adrenal medullae. Nociceptors in the paw were activated by capsaicin and depression of BK-induced PE was measured in rats with intact or cut subdiaphragmatic vagus nerves. After cutting the dorsolateral funiculus (DLF) contralateral to the stimulated hindpaw (segmental level C5/C6 and T8/T9), depression of BK-induced PE was weak or absent both in rats with intact vagus nerves and in vagotomised rats, suggesting that an ascending excitatory pathway was interrupted. After cutting the DLF ipsilateral to the stimulated hindpaw, depression of BK-induced PE was already markedly enhanced, even in the absence of vagotomy. Ipsilateral DLF lesion (L2/L3) below the level of the spinal output to the adrenal medullae produced the same effect, suggesting interruption of a descending inhibitory pathway that relays the effect of vagal activity to the level of the capsaicin-induced nociceptive input. Contralateral and ipsilateral hemisection of the spinal cord (C5/C6) produced the same changes as the corresponding DLF lesions. Ipsi- or contralateral lesion of the dorsal funiculus at the spinal level T8/T9 had no effect on depression of BK-induced PE generated by cutaneous noxious stimulation of the forepaw. We suggest that noxious stimulation activates an ascending pathway of the spino-bulbo-spinal excitatory circuit which projects through the DLF contralateral to the nociceptive input, and that the inhibitory pathway which is activated by vagal afferent activity projects through the DLF ipsilateral to the nociceptive input.

Adrenal Medulla↗

Respiratory rhythmicity in the activity of postganglionic neurones supplying the rat tail during hyperthermia.

It has been suggested that thermoregulatory stimulation changes respiration-related rhythmicity in the activity of postganglionic sympathetic neurones supplying the rat tail to a distinct modulation independent of respiration. To study this possibility, single and few fibre recordings were made from ten filaments split from the ventral collector nerves of the rat during whole body warming. Sympathetic activity was analysed by autocorrelation and phrenic-triggered summation. All neurones except one were gradually inhibited and lost their on-going activity above a core temperature of 39-39.5 degrees C while the frequency of the phrenic bursts increased significantly. During hyperthermia, all neurones tested exhibited a prominent respiratory modulation in their activity which, compared to normothermia, was significantly increased in strength, or even newly acquired. No other rhythm emerged. These results speak against the hypothesis that in the rat sympathetic pathways controlling the tail vasculature and thus involved in thermoregulation, during hyperthermia become controlled by central oscillators distinct from the respiratory rhythm generator. Rather, respiratory modulation appears to remain the dominant rhythm as is common for sympathetic neurones supplying other cardiovascular targets.

Action Potentials↗

Reflex patterns in preganglionic sympathetic neurons projecting to the superior cervical ganglion in the rat.

Reflex patterns in preganglionic neurons projecting in the cervical sympathetic trunk (CST) were analyzed in response to stimulation of various afferent systems. We focused on the question whether these preganglionic neurons can be classified into functionally distinct subpopulations. Reflex responses were elicited by stimulation of trigeminal and spinal nociceptive, thermoreceptive as well as baroreceptor and chemoreceptor afferents. Multi- and single fiber preparations were studied in baroreceptor intact and sino-aortically denervated animals. Spontaneous activity of 36 preganglionic single neurons ranged from 0.2 to 3.5 imp/s (median= 1.11 imp/s). The degree of cardiac rhythmicity (CR) in the activity of sympathetic neurons was 69.5+/-13% (mean+/-S.D.; N=52; range=39-95%). Noxious stimulation of acral skin activated the majority (67%) of sympathetic preparations by 37+/-25% (N=35) above pre-stimulus activity; 15% were inhibited. In these neurons the response to noxious stimulation of acral skin was significantly correlated with the degree of CR (P<0.001, N=52) in that neurons showing the strongest excitation to noxious stimulation displayed the strongest CR. Noxious mechanical stimulation of body trunk skin (N=60) inhibited the majority (80%) of fiber preparations tested (by 34+/-18% of pre-stimulus activity, N=48); an activation was not observed. Cold stimulation of acral (N=9) and body trunk skin (N=42) activated most fiber preparations. Trigeminal stimulation evoked a uniform reflex activation of preganglionic neurons (+79+/-73% of pre-stimulus activity, N=32). Chemoreceptor stimulation by systemic hypercapnia elicited inhibitory (-31+/-19%, N=8) as well as excitatory (+59+/-5%, N=4) responses. These results show that preganglionic sympathetic neurons projecting to target organs in the head exhibit distinct reflex patterns to stimulation of various afferent systems; however, a clear classification into different functional subgroups did not emerge. Furthermore, reflex patterns showed a segmental organization to noxious cutaneous stimulation of acral parts and body trunk reflecting a differential central integration of spinal afferent input. Compared with the cat the reflex organization of sympathetic neurons projecting to the head seems to be less differentiated in the anesthetized rat.

Action Potentials↗

Axotomized and intact muscle afferents but no skin afferents develop ongoing discharges of dorsal root ganglion origin after peripheral nerve lesion.

After peripheral nerve lesions, some axotomized afferent neurons develop ongoing discharges that originate in the dorsal root ganglion (DRG). We investigated in vivo which functional types of afferent neurons contributed to this ectopic activity. Six to twelve days after the gastrocnemius soleus (GS) nerve supplying skeletal muscle and the sural (SU) nerve supplying skin had been transected (experimental group E1), 20.4% of afferent neurons with myelinated axons projecting into the GS nerve produced ongoing discharges of irregular or bursting pattern. In contrast, all SU neurons were silent. Additional transection of peroneal and tibial nerves (group E2) induced ongoing activity in a similar percentage of GS neurons (22.1%), but their mean discharge frequency was higher (6.0 vs 2.7 Hz), and more of them exhibited bursting discharges (63 vs 17%). When the GS nerve had been left intact while tibial, peroneal, and SU nerve had been transected (group E3), 18.8% of unlesioned GS neurons developed ongoing discharges at a mean frequency of 6.1 Hz; most of them exhibited a bursting pattern. Without a preceding nerve lesion, almost no GS neuron (1.1%) fired spontaneously. Most afferent neurons with ongoing activity had an axonal conduction velocity of 5-30 m/sec indicating that some of these neurons may have had nociceptive function. These findings provide the first evidence that after peripheral nerve injury both axotomized as well as intact afferent neurons supplying skeletal muscle but not skin afferents generate ongoing activity within the DRG, probably because of a yet unknown signal in the DRG triggered by axotomy.

Animals↗

The role of vagal visceral afferents in the control of nociception.

We have shown that activity in subdiaphragmatic vagal afferents modulates mechanical hyperalgesic behavior in the rat. Subdiaphragmatic vagotomy decreases paw-withdrawal threshold to mechanical stimulation (baseline and after intradermal injection of bradykinin), thus enhancing mechanical hyperalgesic behavior. Most of this decrease is generated by an endocrine signal released by the adrenal medullae because denervation or removal of the adrenal medullae prevents or reverses these changes. This novel mechanism may imply that: (a) the brain is able to regulate sensitivity of nociceptors all over the body by a neuroendocrine mechanisms, (b) sensitivity of nociceptors can be influenced by changes in parts of the body which are remote from the location of the sensitized nociceptors and (c) circulating catecholamines can influence nociceptors in a way which is different from those reported so far (see Jänig and McLachlan, 1994; Jänig, 1996a; Jänig et al., 1996).

Animals↗

Specificity in the organization of the autonomic nervous system: a basis for precise neural regulation of homeostatic and protective body functions.

Experimental investigations of the lumbar sympathetic outflow to skin, skeletal muscle and viscera and the thoracic sympathetic outflow to the head and neck have shown that each target organ and tissue is supplied by one or two separate pathways which consists of sets of pre- and postganglionic neurons with distinct patterns of reflex activity. This probably applies to all sympathetic and parasympathetic systems. The specificity of the messages that these peripheral pathways transmit from the central nervous system arises from integration within precisely organized pathways in the neuraxis. The messages in these discrete functional pathways are transmitted to the target tissues often via organized neuroeffector junctions. Modulation in the periphery can occur within each pathway, both in ganglia and at the level of the effector organs. This organization is the basis not only for precise neural regulations of all homeostatic body functions in which the autonomic nervous system is involved but also the basis of one main component in the regulation of protective body functions: (a) Elementary defense behaviors which are organized in the mesencephalon (confrontational defense, flight, quiescence), (b) regulation of the immune system by the sympathetic nervous system, and (c) adaptive autonomic motor responses during basic emotions require precisely working autonomic, in particular sympathetic, systems. In this sense, the concept of the functioning of the sympathetic nervous system in an "all-or-none" fashion, without distinction between different effector organs, and of simple functional antagonistic organization between sympathetic and parasympathetic nervous system is misleading, inadequate and untenable.

Animals↗

Sympathetic-sensory coupling after L5 spinal nerve lesion in the rat and its relation to changes in dorsal root ganglion blood flow.

Transection of the L5 spinal nerve in rats results in allodynia- and hyperalgesia-like behavior to mechanical stimulation which are thought to be mediated by ectopic activity arising in lesioned afferent neurons mainly in the dorsal root ganglion (DRG). It has been suggested that the neuropathic pain behavior is dependent on the sympathetic nervous system. In rats 3-56 days after L5 spinal nerve lesion, we tested responses of axotomized afferent fibers recorded in the dorsal root of the lesioned segment to norepinephrine (NE, 0.5 microg/kg) injected intravenously and to selective electrical stimulation of the lumbar sympathetic trunk (LST). In some experiments we measured blood flow in the DRG by laser Doppler flowmetry. The majority of lesioned afferent fibers with spontaneous activity responded to neither LST stimulation (82.4%) nor NE (71.4%). In those which did react to LST stimulation, responses occurred only at high stimulation frequencies (likely to be above the physiological range), and they could be mimicked by non-adrenergic vasoconstrictor drugs (angiotensin II, vasopressin). Excitatory responses to LST stimulation were closely correlated with the stimulation-induced phasic vasoconstrictions in the DRG. We therefore hypothesized that the activation of lesioned afferents might be brought about indirectly by an impaired blood supply to the DRG. To test this hypothesis we induced a strong and sustained baseline vasoconstriction in the DRG by blocking endothelial nitric oxide synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME) applied systemically. L-NAME enhanced baseline vascular resistance in the DRG about threefold and also increased stimulation-induced vasoconstrictions. After L-NAME, the majority of axotomized neurons with spontaneous activity were activated by LST stimulation (76%) or NE (75%). Again, activations closely followed stimulation-induced phasic vasoconstrictions in the DRG provided that a critical level of vasoconstriction was exceeded. In the present study, inhibitory responses to LST stimulation were generally rare and could be reversed to activation by prolonged stimulation or after L-NAME. These results show that sympathetic-sensory coupling occurs only in a minority of axotomized afferents after L5 spinal nerve injury. Like previous studies, they cast doubt on the notion that the L5 spinal nerve lesion is a good model for sympathetically maintained pain. Since responses of lesioned afferent neurons to LST stimulation and NE could be provoked with high reliability after inducing vasoconstriction in the DRG, and since they mirrored stimulation-induced vasoconstrictions in the DRG, it appears that in this model the association of sympathetic activity with afferent discharge occurs mainly when perfusion of the DRG is impaired.

Animals↗

Spontaneous activity of axotomized afferent neurons after L5 spinal nerve injury in rats.

After mechanical injury of a peripheral nerve some axotomized afferent neurons develop spontaneous activity, which is thought to trigger abnormal pain behavior in rats and neuropathic pain in humans. Here, we analysed the ectopic activity in axotomized afferent fibers recorded from the L5 dorsal root in different time periods after L5 spinal nerve lesion and the effects of sympathectomy on it. The following results were obtained: (1) Up to 6 hours after spinal nerve transection there was almost no spontaneous activity in axotomized afferents, except short-lasting injury discharges at the time of transection; (2) Three to 8 days following spinal nerve lesion, the rate of spontaneous activity was 7.3+/-7.7 imp/s (mean+/-SD, median 5.0 imp/s, n=204); 41.6% of the spontaneously active afferent neurons exhibited a bursting pattern with interspike intervals of 32.4+/-18.3 ms; (3) Twenty to 53 days after nerve lesion the rate of spontaneous activity had decreased significantly to 3.4+/-4.3 imp/s (median 2.6 imp/s, n=120). The frequency of bursting and non-bursting neurons remained roughly the same; (4) In sympathectomized rats, 15-45 days following spinal nerve lesion, the mean discharge rate was 3.8+/-4.3 imp/s (median 2. 3 imp/s, n=255). However, the percentage of bursting neurons and the intraburst frequency decreased significantly; (5) Spontaneous activity occurred in afferent A-fibers but not in afferent C-fibers. These results suggest that ectopic activity in axotomized afferent neurons develops within the first days after L5 spinal nerve lesion, decreases with time and is only marginally dependent on the sympathetic innervation. There was a positive correlation between this ectopic activity and the allodynia-like behavior in spinal nerve-lesioned rats.

Animals↗