Sympathetically Independent Pain Research Articles

Changes in Regional Cerebral Blood Flow and Three-Phase Bone Scan After Repeated Somatic Nerve Blocks for Sympathetically Independent Pain

The pathophysiology of complex regional pain syndrome type 1 (CRPS 1) correlates with variances in both the peripheral and central nerve system. We attempted to explore the topographic correlation between changes in regional cerebral blood flow (rCBF) and 3-phase bone scans during treatments of a series of somatic nerve blocks. The case we present here is a 24-year-old man, who suffered CRPS 1 in his right upper extremity for 4 months, and conservative therapy proved to be ineffectual to him. As he did not respond to stellate ganglion block, the syndrome was regarded as sympathetically independent pain (SIP). However, after administering a series of brachial plexus block and local anesthetics, complete resolution of pain, and restoration of function were manifested. In addition, an increase in rCBF, evidenced by single-photon emission computed tomography (SPECT), and changes in the 3 phase bone scan before and after the nerve block appear to correlate well with the clinical improvement. The changes in rCBF seem to support the theory that the pathogenesis of CRPS is also related to the central nervous system. Multiple somatic nerve blocks (SNB) not only improved physical function but also reversed the CRPS symptoms, for which we presume that reduced nociceptive input signals led to cortical reorganization.

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.

Diagnostic and treatment measures in patients with sympathetically maintained pain

The term "sympathetically maintained pain" (SMP) describes a symptom that might accompany a variety of diseases (CRPS, (post-) herpetic and post-injury neuralgia), which might transform into sympathetically independent pain (SIP) after some time. Patients with SMP present a bunch of disorders of the autonomic and sensory system, but the only reliable way to diagnose a pain as SMP is a positive response to an intervention at the sympathetic nervous system. Three ways of influencing the sympathetic system are commonly used: (a) local anesthetic sympathetic blockade (SB), (b) intravenous regional sympathectomy (IVRS) and (c) ganglionic local opioid application (GLOA). A review of current literature shows that SB has certain advantages in diagnostic sensitivity, whereas GLOA might be slightly superior in therapy of some diseases with longstanding pain history. Obviously, the therapeutic benefit of all interventions is complete independent of the accompanying autonomic disorder and of a blockade of efferent fibers. A new heuristic model of the SMP mechanism is presented, including both experimental and clinical data. For reducing the risks of false positive or negative diagnosis of SMP and SIP, a diagnostic algorithm is proposed. This includes optimizing the technique, changes of interventional measures, and adequate monitoring both of analgesia and as well of the extend of efferent sympathetic blockade (e.g. measurement of sympathetic reflexes). The treatment recommendations in patients with SMP vary in dependence of the kind of disease. In SMP, invasive measures play an important, but only limited role within the comprehensive treatment concept. As an example a three-stage, symptom-adapted treatment algorithm is demonstrated for CRPS, including also drug therapy, psychologic and physiotherapeutic approaches.

Effects of regional intravenous guanethidine in patients with neuralgia in the hand; a follow-up study over a decade

A study on the effect of regional intravenous (i.v.) guanethidine blockade (RGB) was done over a 10 years period in patients with post-traumatic neuralgia. Seven patients, investigated with quantitative sensory testing (QST) before and after RGB between 1979 and 1982, were reinvestigated in the period 1990–1992. In addition to the RGB, 6 patients were subjected to a placebo procedure with torniquet inflation and i.v. injection of saline at follow-up. All patients had ongoing pain and stimulus-induced pain (hyperalgesia) in one hand. The QST was done by an independent observer who was blind with regard to the different treatments. Three patients with long-lasting relief of ongoing pain and significant reduction of stimulus-induced pain after RGB, were classified as having sympathetically maintained pain (SMP) both at 1st examination and at follow-up 10 years later. In 2 patients, classified as having sympathetically independent pain (SIP), neither the ongoing pain nor the hyperalgesia improved at any occasion. Two patients, classified as SMP in 1979–1982, changed to SIP at follow-up. Placebo had no significant effect on the hyperalgesia to heat, cold or vibration in the 6 SMP/SIP patients tested. In conclusion, some patients with neuralgia, diagnosed 17–26 years ago, still had long-lasting pain relief from an i.v. RGB, whereas others consistently had no such effect. None obtained long-lasting pain relief from placebo. This supports the notion that different pathophysiological mechanisms are involved in post-traumatic neuralgia.

Sciatic Cryoneurolysis in Rats

The purpose of this study was to evaluate the effects of preemptive and postlesion sympathectomy in the sciatic cryoneurolysis (SCN) model of neuropathic pain in rats.SCN in rats produces a prolonged significant mechanical allodynia (hypersensitivity to previously nonnoxious mechanical stimuli) with no thermal hyperalgesia. In at least two other models, sympathectomy is effective in attenuating existing mechanical allodynia and thermal hyperalgesia or deterring their development after nerve injury. These models appear to mimic the direct sympathetic involvement characteristic of the clinical syndrome termed sympathetically maintained pain (SMP). To investigate these concepts in the SCN model, sympathectomy was performed prior to SCN in animals with established SCN-induced allodynia. Sympathectomy did not alter the pattern of existing allodynia or its development in this model. The results suggest that SCN is a useful and easily reproducible model of sympathetically independent pain (SIP). (Anesth Analg 1995;81:544-8)

Sciatic Cryoneurolysis in Rats

The purpose of this study was to evaluate the effects of preemptive and postlesion sympathectomy in the sciatic cryoneurolysis (SCN) model of neuropathic pain in rats. SCN in rats produces a prolonged significant mechanical allodynia (hypersensitivity to previously non-noxious mechanical stimuli) with no thermal hyperalgesia. In at least two other models, sympathectomy is effective in attenuating existing mechanical allodynia and thermal hyperalgesia or deterring their development after nerve injury. These models appear to mimic the direct sympathetic involvement characteristic of the clinical syndrome termed sympathetically maintained pain (SMP). To investigate these concepts in the SCN model, sympathectomy was performed prior to SCN in animals with established SCN-induced allodynia. Sympathectomy did not alter the pattern of existing allodynia or its development in this model. The results suggest that SCN is a useful and easily reproducible model of sympathetically independent pain (SIP).

Sciatic Cryoneurolysis in Rats

The purpose of this study was to investigate the possibility that sympathetic exacerbation of neuropathic pain activity may be mediated in part by the development of abnormal peripheral adrenergic mechanisms at the site of peripheral nerve injury. We evaluated changes in mechanical stimulation withdrawal thresholds before and after the delivery of selected alpha-adrenergic agonists and antagonists to the immediate area of a prior nerve injury in rats that had developed continuous mechanical allodynia subsequent to sciatic cryoneurolysis (SCN). Allodynia was attenuated (thresholds increased) after administration of the alpha 1 antagonist prazosin, but not the alpha 2 antagonist idazoxan. Similar attenuation occurred with infusions of the alpha 2 agonist dexmedetomidine and at the lowest dose (2.0 micrograms) of the mixed alpha agonist clonidine. In contrast, allodynia was exacerbated (thresholds decreased) by infusion of the highest dose of clonidine (20 micrograms). Infusions of the alpha 2 agonist ST-91, a polar analog of clonidine, did not alter withdrawal thresholds. The findings suggest that a minimal peripheral adrenergic modulation of SCN-induced allodynia occurs via mechanisms that are not localized to the prior injury site. However, overall, the SCN model of neuropathic pain appears to be resistant to adrenergic interventions, providing further evidence that SCN in rats is a model of sympathetically independent pain (SIP).

Sciatic Cryoneurolysis in Rats

The purpose of this study was to investigate the possibility that sympathetic exacerbation of neuropathic pain activity may be mediated in part by the development of abnormal peripheral adrenergic mechanisms at the site of peripheral nerve injury.We evaluated changes in mechanical stimulation withdrawal thresholds before and after the delivery of selected alpha-adrenergic agonists and antagonists to the immediate area of a prior nerve injury in rats that had developed continuous mechanical allodynia subsequent to sciatic cryoneurolysis (SCN). Allodynia was attenuated (thresholds increased) after administration of the alpha1 antagonist prazosin, but not the alpha2 antagonist idazoxan. Similar attenuation occurred with infusions of the alpha2 agonist dexmedetomidine and at the lowest dose (2.0 micro gram) of the mixed alpha agonist clonidine. In contrast, allodynia was exacerbated (thresholds decreased) by infusion of the highest dose of clonidine (20 micro gram). Infusions of the alpha2 agonist ST-91, a polar analog of clonidine, did not alter withdrawal thresholds. The findings suggest that a minimal peripheral adrenergic modulation of SCN-induced allodynia occurs via mechanisms that are not localized to the prior injury site. However, overall, the SCN model of neuropathic pain appears to be resistant to adrenergic interventions, providing further evidence that SCN in rats is a model of sympathetically independent pain (SIP). (Anesth Analg 1995;81:549-54)

Quantitative sensory tests in patients with neuralgia 11 to 25 years after injury

In a previous study quantitative sensory tests were used to characterize the symptoms in patients with post-traumatic neuralgia in the hand. Two types of pain syndromes were identified, sympathetically maintained pain (SMP), and sympathetically independent pain (SIP). These two syndromes had different sensory profiles with regard to temperature discrimination and cold and heat pain thresholds. The aim of the present study was to investigate the development of symptoms 10 years later. Eighteen previously investigated patients were contacted and all answered questions concerning their symptoms. Of these, two SIP and eight SMP patients agreed to undergo quantitative sensory testing. The outcome of these tests and the patients' own reports indicated that patients with SMP, who were not repeatedly treated with sympathetic blocks, did not show any remarkable spontaneous improvement of symptoms over a decade. The SMP patients still exhibited their characteristic sensory profile with moderate impairment of temperature discrimination and allodynia to cold, heat and vibratory stimuli. However, some changes with time were observed with respect to warm-cold difference limen and vibration allodynia. Comparison with data obtained from an age-matched group of healthy individuals indicated that these changes were due to age-related factors.

Quantitative sensory testing before and after regional guanethidine block in patients with neuralgia in the hand

Using reference values from healthy volunteers, thermal and vibration-induced pain thresholds and the sensibility for warm and cold were studied in 18 patients with neuralgia in one hand following a traumatic injury or surgery. All patients had spontaneous pain and allodynia to vibration. They were treated with intravenous regional guanethidine block (RGB). Quantitative sensory testing was performed on both hands before and 1–3 days after treatment. Eleven patients benefitted considerably from the block, with pain relief for 2 weeks or more. Ten of these 11 patients had mild nerve injuries caused by compressive trauma to the nerve. Before RGB they showed a moderate loss in temperature discrimination capacity; their heat pain thresholds were reduced and they exhibited allodynia to cold and vibration on the injured side. After RGB, the pain thresholds were normalised both to thermal and vibratory stimuli. These patients were classified as having sympathetically maintained pain (SMP). Seven patients reported no or only minor pain-relieving effect of RGB lasting 1–5 days. Severe nerve injuries were most frequent in this group of patients. On the injured side, before RGB, their ability to discriminate between warm and cold was markedly impaired, thermal pain thresholds were normal, and they showed allodynia to vibration. After RGB, there was no change in thermal pain thresholds and the allodynia to vibration persisted. These patients were classified as having sympathetically independent pain (SIP). The results indicate that quantitative thermal sensory tests, together with clinical evaluation of the nerve trauma, can help to predict which patients will have long-lasting pain alleviation after RGB treatment.