Sympathetically Maintained Pain Research Articles

Oral Squamous Cell Carcinoma Induces Nerve Injury And Adrenergic Receptor Plasticity Resulting In Sympathetically-Maintained Pain

Oral Squamous Cell Carcinoma Induces Nerve Injury And Adrenergic Receptor Plasticity Resulting In Sympathetically-Maintained Pain

Investigation of the Sympathetic Regulation in Delayed Onset Muscle Soreness: Results of an RCT.

Sports-related pain and injury is directly linked to tissue inflammation, thus involving the autonomic nervous system (ANS). In the present experimental study, we disable the sympathetic part of the ANS by applying a stellate ganglion block (SGB) in an experimental model of delayed onset muscle soreness (DOMS) of the biceps muscle. We included 45 healthy participants (female 11, male 34, age 24.16 ± 6.67 years [range 18–53], BMI 23.22 ± 2.09 kg/m2) who were equally randomized to receive either (i) an SGB prior to exercise-induced DOMS (preventive), (ii) sham intervention in addition to DOMS (control/sham), or (iii) SGB after the induction of DOMS (rehabilitative). The aim of the study was to determine whether and to what extent sympathetically maintained pain (SMP) is involved in DOMS processing. Focusing on the muscular area with the greatest eccentric load (biceps distal fifth), a significant time × group interaction on the pressure pain threshold was observed between preventive SGB and sham (p = 0.034). There was a significant effect on pain at motion (p = 0.048), with post hoc statistical difference at 48 h (preventive SGB Δ1.09 ± 0.82 cm VAS vs. sham Δ2.05 ± 1.51 cm VAS; p = 0.04). DOMS mediated an increase in venous cfDNA -as a potential molecular/inflammatory marker of DOMS- within the first 24 h after eccentric exercise (time effect p = 0.018), with a peak at 20 and 60 min. After 60 min, cfDNA levels were significantly decreased comparing preventive SGB to sham (unpaired t-test p = 0.008). At both times, 20 and 60 min, cfDNA significantly correlated with observed changes in PPT. The 20-min increase was more sensitive, as it tended toward significance at 48 h (r = 0.44; p = 0.1) and predicted the early decrease of PPT following preventive stellate blocks at 24 h (r = 0.53; p = 0.04). Our study reveals the broad impact of the ANS on DOMS and exercise-induced pain. For the first time, we have obtained insights into the sympathetic regulation of pain and inflammation following exercise overload. As this study is of a translational pilot character, further research is encouraged to confirm and specify our observations.

Alpha 1 adrenoceptor expression in skin, nerves and blood vessels of patients with painful diabetic neuropathy.

Diabetic neuropathy (dNP) patients often suffer from severe neuropathic pain. It was suggested that alpha-1 adrenoceptor (α1-AR) hyperresponsiveness contributes to pain in dNP. The aim of our study was to quantify α1-AR expression using immunohistochemistry in skin biopsies of nine patients with painful diabetic neuropathy compared to 10 healthy controls. Additionally, the association between α1-AR expression and activation with spontaneous and sympathetically maintained pain (SMP) induced by intradermal injection of the α1-agonist phenylephrine was investigated. For control purposes the α2-agonist clonidine was injected in a different session. We found that dermal nerve density was significantly lower in dNP than in controls. However, α1-AR expression was significantly greater on cutaneous blood vessels and keratinocytes of dNP patients than controls. A similar trend, which failed to reach significance, was observed for dermal nerves. Intradermal injection of phenylephrine induced only minor pain, which resolved after a few minutes. Adrenergically evoked pain persisted for more than 15min in only one patient, but none of the patients fulfilled the criteria for SMP (pain increase after injection of phenylephrine and decrease after clonidine). In conclusion, our results imply that SMP does not occur in dNP. However, elevated expression of α1-AR on keratinocytes and dermal blood vessels is an important finding, since this could contribute to dNP progression and supports the theory of receptor up-regulation of denervated structures. The implications of this α1-upregulation should be examined in further studies.

Incidence of inadvertent intercostal or epidural spread during thoracic sympathetic ganglion block

BackgroundSympathetic blocks (SBs) have been used widely to relieve the symptoms of sympathetically maintained pain (SMP). The thoracic sympathetic ganglion is not separated from somatic nerves by muscles and connective tissue. The upper thoracic ganglion runs along the posterior surface of the vertebral column in close proximity to the adjacent epidural region. This anatomical difference leads to frequent epidural and intercostal spread in cases of thoracic SBs. The purpose of this study was to investigate the incidence of inadvertent intercostal and epidural injections during thoracic SBs.MethodsTwenty-two patients who were suffering from complex regional pain syndrome or lymphedema after breast cancer surgery were managed with two or three times of thoracic SBs. Therefore, injections of 63 thoracic SBs from 22 patients were enrolled in this study. An investigator who did not attend the procedure evaluated the occurrence of intercostal or epidural spread using anteroposterior fluoroscopic images.ResultsThe overall incidence of inadvertent intercostal or epidural spread of contrast was 47.5%. Among the inadvertent injections, intercostal spread (34.9%) was more frequent than epidural spread (12.6%). Only 52.5% of the thoracic SBs demonstrated successful contrast spread without any inadvertent spread. The mean difference in skin temperature between the blocked and unblocked sides was 2.5 ± 1.8ºC. Fifty-nine (93.6%) injections demonstrated more than 1.5ºC difference.ConclusionsThoracic SBs showed a high incidence (47.5%) of inadvertent epidural or intercostal injection. Thus, special attention is required for the diagnosis of SMP or the injection of any neurolytic agent around sympathetic ganglion.

Decreased neural expression of the noradrenaline transporter in the papillary dermis after partial sciatic nerve lesion

After peripheral nerve injury, regeneration or collateral sprouting of noradrenergic nerve fibres in the papillary dermis of the injured limb may contribute to sympathetically-maintained pain. The aim of this study was to determine whether noradrenergic nerve fibre regeneration after partial sciatic nerve ligation (PSL) in Wistar rats was accompanied by parallel shifts in expression of the noradrenaline transporter (NAT). Four or 28 days after PSL surgery, immunohistochemistry was used to examine NAT expression in plantar hind paw skin in relation to pan-neuronal markers (class III beta-tubulin and protein gene product 9.5), peptidergic afferents containing calcitonin gene-related peptide (CGRP), nonpeptidergic afferents labelled by isolectin B4 (IB4), and tyrosine hydroxylase (TH), a marker for cutaneous noradrenergic nerve fibres. Most dermal nerve fibre populations decreased shortly after PSL. However, four weeks after PSL, an increase in staining intensity of CGRP and novel expression of TH were observed in the papillary dermis on the injured side. In contrast, neural expression of NAT was reduced in this region. Loss of NAT might have implications for sympathetically-maintained pain, as failure to rapidly clear noradrenaline could exacerbate aberrant sympathetic-sensory signalling between closely apposed noradrenergic and peptidergic nerve fibres.

Bimodal Modulation of Ipsilateral Spinal-Coeruleo-Spinal Pathway in CRPS: A Novel Model for Explaining Different Clinical Features of the Syndrome.

The objective is to present a hypothesis to explain the sensory, autonomic, and motor disturbances associated with complex regional pain syndrome (CRPS) syndrome. The author reviewed the available and relevant literature, which was supplemented with research on experimental animal models, with a focus on how they may translate into humans, particularly in areas about pathophysiologic mechanisms of CRPS. We propose that different CRPS subtypes may result from facilitative or inhibitory influences exerted by the spinal-coeruleo-spinal pathway in three sites at the spinal cord: the dorsal horn (DH), intermediolateral cell column (IML) and ventral horn (VH). A facilitatory influence over DH may have a pronociceptive effect that explains exacerbated pain, sensory disturbances, and spreading sensitization and neuroinflammation. Conversely, a facilitatory influence over preganglionic neurons located in IML cell column may increase sympathetic outflow with peripheral vasoconstriction, which leads to cold skin, ipsilateral limb ischaemia, and sympathetically maintained pain (SMP). For patients presenting with these symptoms, a descending inhibitory influence would be predicted to result in decreased sympathetic outflow and warm skin, as well as impairment of peripheral vasoconstrictor reflexes. Finally, a descending inhibitory influence over VH could explain muscle weakness and decreased active range of motion, while also facilitating motor reflexes, tremor and dystonia. The proposed model provides a mechanistically based diagnostic scheme for classifying and explaining the sensory, autonomic and motor disturbances associated with CRPS syndrome.

Local Anesthetic Sympathectomy Restores fMRI Cortical Maps in CRPS I after Upper Extremity Stellate Blockade: A Prospective Case Study

Background: Patients with complex regional pain syndrome type I (CRPS I) show a cortical reorganization with contralateral shrinkage of cortical maps in S1. The relevance of pain and disuse for the development and the maintenance of this shrinkage is unclear. Objective: Aim of the study was to assess whether short-term pain relief induces changes in the cortical representation of the affected hand in patients with CRPS type I. Study Design: Case series analysis of prospectively collected data. Methods: We enrolled a case series of 5 consecutive patients with CRPS type I (disease duration 3 – 36 months) of the non-dominant upper-limb and previously diagnosed sympathetically maintained pain (SMP) by reduction of the pain intensity of more than > 30% after prior diagnostic sympathetic block. We performed fMRI for analysis of the cortical representation of the affected hand immediately before as well as one hour after isolated sympathetic block of the stellate ganglion on the affected side. Statistics: Wilcoxon-Test, paired t-test, P < 0.05. Results: Pain decrease after isolated sympathetic block (pain intensity on the numerical rating scale (0 – 10) before block: 6.8 ± 1.9, afterwards: 3.8 ± 1.3) was accompanied by an increase in the blood oxygenation level dependent (BOLD) response of cortical representational maps only of the affected hand which had been reduced before the block, despite the fact that clinical and neurophysiological assessment revealed no changes in the sensorimotor function. Limitations: The interpretation of the present results is partly limited due to the small number of included patients and the missing control group with placebo injection. Conclusions: The association between recovery of the cortical representation and pain relief supports the hypothesis that pain could be a relevant factor for changes of somatosensory cortical maps in CRPS, and that these are rapidly reversible. Key words: Cortical reorganization, cortical plasticity, cortical maps, complex regional pain syndrome (CRPS), sympathetically maintained pain (SMP), sympathetic block (SB)

Inflammation in CRPS: Role of the sympathetic supply

Acute Complex Regional Pain Syndrome (CRPS) is associated with signs of inflammation such as increased skin temperature, oedema, skin colour changes and pain. Pro-inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin-2 (IL-2), IL-1beta, IL-6) are up-regulated, whereas anti-inflammatory cytokines (IL-4, IL-10) are diminished. Adaptive immunity seems to be involved in CRPS pathophysiology as many patients have autoantibodies directed against β2 adrenergic and muscarinic-2 receptors. In an animal tibial fracture model changes in the innate immune response such as up-regulation of keratinocytes are also found. Additionally, CRPS is accompanied by increased neurogenic inflammation which depends mainly on neuropeptides such as CGRP and Substance P. Besides inflammatory signs, sympathetic nervous system involvement in CRPS results in cool skin, increased sweating and sympathetically-maintained pain. The norepinephrine level is lower in the CRPS-affected than contralateral limb, but sympathetic sprouting and up-regulation of alpha-adrenoceptors may result in an adrenergic supersensitivity. The sympathetic nervous system and inflammation interact: norepinephrine influences the immune system and the production of cytokines. There is substantial evidence that this interaction contributes to the pathophysiology and clinical presentation of CRPS, but this interaction is not straightforward. How inflammation in CRPS might be exaggerated by sympathetic transmitters requires further elucidation.

Testing the Link between Sympathetic Efferent and Sensory Afferent Fibers in Neuropathic Pain

The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic α-adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done inrandom order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25-35 mg). The pain relief achieved by LASB and PhB correlated closely (r = 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t = 0.19, P > 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that α-adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP.

Using an n-of-1 trial to assist in clinical decision making for patients with orofacial pain

Many orofacial pain problems are relatively easy to diagnose and can be treated successfully, but unfortunately some are not. One poorly understood pain condition, especially when it presents in the head and neck region, is complex regional pain syndrome (CRPS). Diagnosing CRPS based on history and physical examination alone can be problematic1. Obtaining a diagnosis based on the underlying mechanism is thought to be ideal2, but that often is not possible. Since some patients with CRPS also suffer from sympathetically maintained pain (SMP), sympathetic blockade with local anesthetic has been suggested to determine how that procedure affects the patient’s experience of pain3. However, positive responses may occur due to non-specific treatment effects (e.g., placebo) – especially when it comes to pain reduction with interventions4,5. Since the prevalence of head and neck CRPS is extremely low, with only about 14 cases reported6, false-positive diagnostic test results are to be expected. Also, the diagnostic sensitivity and specificity of sympathetic blocks are unknown but thought to be variable7, and this may change in the course of CRPS, making it difficult to draw definitive conclusions from such tests. This paper discusses an alternative approach to this dilemma, using a research-based technique to solve a single-patient problem.

Are Sympathetic Blocks Useful for Diagnostic Purposes?

Sympathetically maintained pain (SMP) can occur in patients with neuropathic pain. Sympathetically maintained pain is frequently diagnosed clinically by assessing the analgesic effect of an appropriate sympathetic block (SB). The diagnostic value of such blocks depends on both the degree of sympathetic activity disruption achieved and its duration without unintentional concomitant sensory block. This pilot study evaluated the rate of diagnostically valuable SBs performed by experienced anesthesiologists in 19 patients (stellate/thoracic blocks: n = 11, lumbar blocks: n = 12). Monitoring included pain rating before SB; 10 and 30 minutes; and at 1, 3, and 6 hours after SB; bilateral skin temperature 30 minutes before SB through 120 minutes after SB; and detection of bilateral thresholds for cold, warmth, tactile, and vibration stimuli before and after. Ten (43%) of 23 SBs were not eligible for SMP diagnosis (4 had insufficient skin temperature increase; and 6 had cold or tactile detection threshold increases in the painful area). In 11 of the SBs, no significant sensory threshold change was detected; however, 2 individuals demonstrated marked reductions in the cold or tactile sensory thresholds. Sympathetically maintained pain was diagnosed in 3 (25%) of the 12 patients who had at least 1 SB with the required skin temperature increase without concomitant somatosensory block. Sympathetic blocks are useful in the diagnosis of SMP. However, their value is limited by the potential for false positives (unintentional sensory block) or false negatives (insufficient SB). Adequate monitoring of the sympathetic and somatosensory function for a minimum of 90 minutes after the intervention is essential to ensure that a valid diagnosis of SMP is made.

Sensory Disturbances in Complex Regional Pain Syndrome: Clinical Observations, Autonomic Interactions, and Possible Mechanisms

To review mechanisms that might contribute to sensory disturbances and sympathetically-maintained pain in complex regional pain syndrome (CRPS). CRPS is associated with a range of sensory and autonomic abnormalities. In a subpopulation of patients, sympathetic nervous system arousal and intradermal injection of adrenergic agonists intensify pain. Mechanisms responsible for sensory abnormalities in CRPS include sensitization of primary afferent nociceptors and spinothalamic tract neurons, disinhibition of central nociceptive neurons, and reorganization of thalamo-cortical somatosensory maps. Proposed mechanisms of sympathetically-maintained pain include adrenergic excitation of sensitized nociceptors in the CRPS-affected limb, and interaction between processes within the central nervous system that modulate nociception and emotional responses. Central mechanisms could involve adrenergic facilitation of nociceptive transmission in the dorsal horn or thalamus, and/or depletion of bulbo-spinal opioids or tolerance to their effects. Sympathetic neural activity might contribute to pain and sensory disturbances in CRPS by feeding into nociceptive circuits at the site of injury or elsewhere in the CRPS-affected limb, within the dorsal horn, or via thalamo-cortical projections.

UNRAVELLING THE PATHOPHYSIOLOGY OF COMPLEX REGIONAL PAIN SYNDROME: FOCUS ON SYMPATHETICALLY MAINTAINED PAIN

1. In diseases such as complex regional pain syndrome (CRPS), where neuropathic pain is the primary concern, traditional pain classifications and lesion descriptors are of limited value. To obtain better treatment outcomes for patients, the underlying pathophysiological mechanisms of neuropathic pain need to be elucidated and analysed so that therapeutic targets can be identified and specific treatments developed. 2. In the present review, we examine the current literature on sympathetically maintained pain (SMP), a subset of neuropathic pain, within the context of CRPS. Evidence from both human and animal studies is presented and discussed in terms of its support for the existence of SMP and the mechanistic information it provides. 3. We discuss three current hypotheses that propose both a site and method for sympathetic-sensory coupling: (i) direct coupling between sympathetic and sensory neurons in the dorsal root ganglion; (ii) chemical coupling between sympathetic and nociceptive neuron terminals in skin; and (iii) the development of a-adrenoceptor-mediated supersensitivity in nociceptive fibres in skin in association with the release of inflammatory mediators. 4. Finally, we propose a new hypothesis that integrates the mechanisms of chemical coupling and a-adrenoceptor-mediated supersensitivity. This hypothesis is based on previously unpublished data from our laboratory showing that a histological substrate suitable for sympathetic-sensory coupling exists in normal subjects. In the diseased state, the nociceptive fibres implicated in this substrate may be activated by both endogenous and exogenous noradrenaline. The mediating a-adrenoceptors may be expressed on the nociceptive fibres or on closely associated support cells.

Norepinephrine-induced nociception and vasoconstrictor hypersensitivity in rats with chronic post-ischemia pain

Painful hypersensitivity to norepinephrine (NE) has been reported in various chronic pain conditions that exhibit sympathetically-maintained pain (SMP), particularly CRPS-I and II. We investigated the parallels between the nociceptive and vascular sensitivity to NE in rats with chronic post-ischemia pain (CPIP), an animal model of CRPS-I induced by hind paw ischemia–reperfusion injury. Intradermal injections of NE to the affected hind paw induced dose-dependent nociceptive behaviours in CPIP rats, but not sham animals. These behaviours were blocked by α 1- and α 2-adrenergic receptor antagonists, or a nitric oxide (NO) donor. Using laser Doppler flowmetry, we detected vasoconstrictor hypersensitivity in the ipsilateral CPIP hind paw, as compared to responses in sham animals or the contralateral hind paw. The vasoconstrictor hypersensitivity was also attenuated by adrenergic antagonists. Intradermal injection of [Arg 8] vasopressin (AVP) or the endothelial NO synthase (eNOS) inhibitor, l-NIO, to the affected paw also induced nociceptive behaviours in CPIP rats, but not sham rats. These results suggest CPIP rats display abnormal nociceptive responses to adrenergic and non-adrenergic vasoconstrictive agents. Furthermore, the nociceptive responses to NE in CPIP rats are paralleled by enhanced vasoconstrictive responses to NE, and are relieved by α-adrenergic antagonists or a vasodilator. We conclude that persistent tissue ischemia and hypersensitivity to sympathetic vasoconstriction are important mechanisms for pain in CPIP rats, and that either reducing vasoconstriction or enhancing vasodilatation may be effective methods of relieving the pain of CRPS-I.

Thoracic Outlet Syndrome: A 50-Year Experience at Baylor University Medical Center

During the past 5 decades, the recognition and management of thoracic outlet syndrome (TOS) have evolved. This article elucidates these changes and improvements in the diagnosis and management of TOS at Baylor University Medical Center. The most remarkable change over the past 50 years is the use of nerve conduction velocity to diagnose and monitor patients with nerve compression. Recognition that procedures such as breast implantation and median sternotomy may produce TOS has been revealing. Prompt thrombolysis followed by surgical venous decompression for Paget-Schroetter syndrome has markedly improved results compared with the conservative anticoagulation approach; thrombolysis and prompt first rib resection is the optimal treatment for most patients with Paget-Schroetter syndrome. Complete first rib extirpation at the initial procedure markedly reduces the incidence of recurrent neurologic symptoms or the need for a second procedure. Chest pain or pseudoangina can be caused by TOS. Dorsal sympathectomy is helpful for patients with sympathetic maintained pain syndrome or causalgia and patients with recurrent TOS symptoms who need a second procedure.

Antiallodynic Effect of Pregabalin in Rat Models of Sympathetically Maintained and Sympathetic Independent Neuropathic Pain

Pregabalin binds to the voltage-dependent calcium channel α2δ subunit and modulates the release of neurotransmitters, resulting in analgesic effects on neuropathic pain. Neuropathic pain has both sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) components. We studied the antiallodynic effects of pregabalin on tactile allodynia (TA) and cold allodynia (CA) in SMP-and SIP-dominant neuropathic pain models. Allodynia was induced by ligation of the L5 & L6 spinal nerves (SMP model) or by transection of the tibial and sural nerves (SIP model) in rats. For intrathecal drug administration, a PE-10 catheter was implanted through the atlantooccipital membrane to the lumbar enlargement. Pregabalin was administered either intraperitoneally (IP) or intrathecally (IT) and dosed up incrementally until an antiallodynic effect without sedation or motor impairment was apparent. TA was assessed using von Frey filaments, and CA was assessed using acetone drops. IP-administered pregabalin dose-dependently attenuated TA in both models and CA in the SMP model, but not CA in the SIP model. IT-administered pregabalin dose-dependently attenuated both TA and CA in both models. However, the dose response curve of IT-administered pregabalin in SMP was shifted to left from that of SIP and the ED50 of IT-administered pregabalin for CA in SMP was about 900 times less than that in SIP. These findings suggest that pregabalin exerts its antiallodynic effect mainly by acting at the spinal cord, and that IT-administered pregabalin has more potent antiallodynic effects in SMP. The α2δ subunit might be less involved in the CA in SIP.

Preparation of a Clonidine Ointment and its Application to Sympathetically Maintained Pain (SMP)

To treat sympathetically maintained pain (SMP),we prepared an ointment containing clonidine hydrochloride,an α adrenergic agonist,as an in-hospital preparation and observed SMP alleviation in patients treated with it.No redness or other abnormalities were observed in the ointment application area,and there was no blood pressure fall,a pharmacological effect of orally administered clonidine.Plasma clonidine concentrations after applying the ointment were 40 -80 pg/mL,which were sufficiently lower than those required for blood pressure control.These results suggest that clonidine ointment is safe and effective against SMP.It can be used at home and is therefore useful for improving the quality of life (QOL) of patients with chronic pain.

Complex Regional Pain Syndromes

Complex regional pain syndromes (CRPS) can be relieved by sympathetic blockade. Different sympathetic efferent output channels innervate distinct effector organs (ie, cutaneous vasoconstrictor, muscle vasoconstrictor. and sudomotor neurons, as well as neurons innervating deep somatic tissues like bone, joints, and tendons). The aim of the present study was to elucidate in CRPS patients the sympathetically maintained pain (SMP) component that exclusively depends on cutaneous sympathetic activity compared with the SMP depending on the sympathetic innervation of deep somatic tissues. The sympathetic outflow to the painful skin was modulated selectively in awake humans. High and low cutaneous vasoconstrictor activity was produced in 12 CRPS type 1 patients by whole-body cooling and warming (thermal suit). Spontaneous pain was quantified during high and low cutaneous vasoconstrictor activity. By comparing the cutaneous SMP component with the change in pain that was achieved by modulation of the entire sympathetic outflow (sympathetic ganglion block), the SMP component originating in deep somatic structures was estimated. The relief of spontaneous pain after sympathetic blockade was more pronounced than changes in spontaneous pain that could be induced by selective sympathetic cutaneous modulation. The entire SMP component (cutaneous and deep) changes considerably over time. It is most prominent in the acute stages of CRPS. Sympathetic afferent coupling takes place in the skin and in the deep somatic tissues, but especially in the acute stages of CRPS, the pain component that is influenced by the sympathetic innervation of deep somatic structures is more important than the cutaneous activation. The entire sympathetic maintained pain component is not constant in the course of the disease but decreases over time.

An Electrophysiological Approach to the Evaluation of Regional Sympathetic Dysfunction: A Proposed Classifi cation

The importance to physicians of maintaining a level of understanding of illnesses and their treatment continues to reveal itself in a most striking fashion when it comes to the progressive interest recently directed to disorders of the autonomic nervous system (ANS). In particular, the relevance to pain practitioners of disease states which directly involve the sympathetic portion of the ANS has increased markedly following the international renaming of reflex sympathetic dystrophy (RSD) and causalgia to complex regional pain syndrome (CRPS) Type I and Type II respectively, as well as sympathetically maintained pain (SMP). Subsequently it has become better understood that many other forms of neuropathic pain also demonstrate local abnormalities of the sympathetic nervous supply to the skin within the painful territory, thereby increasing the diagnostic value of these (often subtle) cutaneous clinical signs. The objectives of this presentation include (a) a concise review of laboratory tests that are currently used in the evaluation of the autonomic nervous system, (b) a discussion of those procedures that were developed for the assessment of sympathetic sudomotor function, (c) a review of the anatomic pathways subserving those electrophysiological methods for sudomotor testing, and (d) the current diagnostic classification for regional abnormalities of sympathetic sudomotor dysfunction. Methods used in the preparation of this article have included a review of (a) historic clinical and laboratory articles (or translations thereof) regarding the medical importance of disorders of the autonomic nervous system, dating back to more than 155 years ago (b) anatomic and electrophysiological basis for electroneurodiagnostic sudomotor testing, and (c) the author's proposal for a diagnostic classification of regional sympathetic sudomotor dysfunction.

Does the Tibial and Sural Nerve Transection Model Represent Sympathetically Independent Pain?

Neuropathic pain can be divided into sympathetically maintained pain (SMP) and sympathetically independent pain (SIP). Rats with tibial and sural nerve transection (TST) produce neuropathic pain behaviors, including spontaneous pain, tactile allodynia, and cold allodynia. The present study was undertaken to examine whether rats with TST would represent SMP- or SIP-dominant neuropathic pain by lumbar surgical sympathectomy. The TST model was generated by transecting the tibial and sural nerves, leaving the common peroneal nerve intact. Animals were divided into the sympathectomy group and the sham group. For the sympathectomy group, the sympathetic chain was removed bilaterally from L2 to L6 one week after nerve transection. The success of the sympathectomy was verified by measuring skin temperature on the hind paw and by infra red thermography. Tactile allodynia was assessed using von Frey filaments, and cold allodynia was assessed using acetone drops. A majority of the rats exhibited withdrawal behaviors in response to tactile and cold stimulations after nerve stimulation. Neither tactile allodynia nor cold allodynia improved after successful sympathectomy, and there were no differences in the threshold of tactile and cold allodynia between the sympathectomy and sham groups. Tactile allodynia and cold allodynia in the neuropathic pain model of TST are not dependent on the sympathetic nervous system, and this model can be used to investigate SIP syndromes.