Microneurography and Spinal Cord Stimulation in Chronic Visceral Pain
| Status: | Terminated |
|---|---|
| Conditions: | Chronic Pain, Chronic Pain |
| Therapuetic Areas: | Musculoskeletal |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 4/17/2018 |
| Start Date: | February 2008 |
| End Date: | January 23, 2009 |
Autonomic Function Testing and Spinal Cord Stimulation: Implications for Successful Therapy in Chronic Visceral Pain
The purpose of this study is to assess the effect of the spinal cord stimulator (A small wire
is surgically implanted under the skin. Low-level electrical signals are then transmitted
through the lead to the spinal cord to alleviate pain. Using a magnetic remote control, the
patients can turn the current on and off, or adjust the intensity.) on the autonomic nervous
system (sympathetic and parasympathetic). Some studies support that the spinal cord
stimulation suppresses or decreases sympathetic outflow (the sympathetic nervous system is
the one that provide us with the "flight and fight response" and the parasympathetic nervous
system is the one that works while we "sleep, rest and digest".). The sympathetic nervous
system is important in blood pressure regulation also. However, there are not reports
regarding the effect of the spinal cord stimulation on blood pressure regulation in chronic
visceral pain patients. Most clinical trials are focus on the effect of the spinal cord
stimulation on pain relief. We think we could use blood pressure, heart rate and special
analysis of these signals and their relationship to other pain measurements to assess the
effect of the spinal cord stimulation in an objective way.
is surgically implanted under the skin. Low-level electrical signals are then transmitted
through the lead to the spinal cord to alleviate pain. Using a magnetic remote control, the
patients can turn the current on and off, or adjust the intensity.) on the autonomic nervous
system (sympathetic and parasympathetic). Some studies support that the spinal cord
stimulation suppresses or decreases sympathetic outflow (the sympathetic nervous system is
the one that provide us with the "flight and fight response" and the parasympathetic nervous
system is the one that works while we "sleep, rest and digest".). The sympathetic nervous
system is important in blood pressure regulation also. However, there are not reports
regarding the effect of the spinal cord stimulation on blood pressure regulation in chronic
visceral pain patients. Most clinical trials are focus on the effect of the spinal cord
stimulation on pain relief. We think we could use blood pressure, heart rate and special
analysis of these signals and their relationship to other pain measurements to assess the
effect of the spinal cord stimulation in an objective way.
Spinal Cord Stimulation (SCS) has been used since 1967 for the treatment of pain: complex
regional pain syndromes 1 , ischemic limb pain 2-5, failed back surgery syndrome 6, 7, and
refractory angina pectoris 8-11. Recently, Kapural et al. reported a case series of six
patients that underwent SCS for the treatment of chronic visceral pain (CVP)12, 13. SCS
reduced 50% of the patients' pain and improved patient functionality by 60% 14 . Animal
studies suggested that dorsal column pathways are involved in the transmission of visceral
pain 12, 13. Clinical studies in patients with visceral cancer have shown that interruption
of the fibers of the dorsal columns that ascend close to the midline of the spinal cord
significantly relieves pain and decreases analgesic requirement 15-18. Different studies
support the hypothesis that visceral pain perception is positively modulated by the
descending pathways from the medulla. Dorsal column lesion leads to a reduction of thalamic
activation by visceral stimuli and decreased visceral pain perception 19. Visceral
innervation occurs via sympathetic and parasympathetic pathways; parasympathetic afferents
enter the vagal afferents carrying nociceptive information enter trunks while sympathetic
afferents carrying nociceptive information enter at the levels T6 and L3. Therefore, limited
case series using SCS for CVP suggested that pain relief was achieved by blocking these
segments suppressing sympathetic outflow to the abdomen and pelvis 14. The relationship
between autonomic nervous system (ANS) and pain are poorly understood. Animal and clinical
research has provided evidence for close interaction between pain modulatory systems and the
ANS 20, 21. However, little is known about the ANS function in chronic pain patients. Our
previous funded work suggested that chronic low back pain (CLBP) patients have reduced LFRRI
(heart rate variability-low frequency) (not increased as expected) and that indices of the
vagal component of the Heart Rate Variability(HRV) (Root Mean Square of the Successive
Differences (RMSSD), heart rate variability-high frequency (HFRRI) were also attenuated. The
sympatho-vagal balance (LFRRI /HFRRI), a ratio of LF to HF which correlates with higher
sympathetic activation 22, was paradoxically increased 23. We previously demonstrated that
Low Frequency Systolic Blood Pressure (LFSBP) correlates with muscle sympathetic nerve
traffic during orthostatic load supported by a simplified model of blood pressure variability
24. We also showed that LFSBP can be abolished by ganglionic blockade demonstrating the
neurogenic origin of these oscillations in blood pressure 25. Additionally, our study
revealed decreased baroreflex indices (αHF and BRSLF) during sitting in CLBP patients. Blood
pressure was not different in CLBP patients, but there was a trend for higher heart rates
possibly caused by higher sympathetic activity to the heart. These findings of reduced
baroreflex sensitivity and changes in heart rate support hypothesized alterations in
cardio-vagal control in patients with chronic pain 26, 27. In summary, sympathetic function
has been assessed by indirect measures. There is no data available regarding the direct
assessment of sympathetic outflow in CVP patients. Sympathetic outflow is stimulus specific
28, 29. Therefore, the characterization of resting sympathetic outflow and stimulus-induced
sympathetic adjustments requires simultaneous measurements of activity by different
techniques. We propose using microneurography to assess the sympathetic function on a
second-to-second basis in CVP patients. Microneurography directly assess muscle sympathetic
nerve activity (MSNA). This technique is used to define sympathetic responses to a number of
standard physiologic maneuvers. It was first developed in Sweden by Wallin, who described the
technique for recording afferent muscle or skin sympathetic nerve activity 30, 31. MSNA
displays real-time sympathetic nerve activity, allowing definition of sympathetic responses
so transient that they would be lost to all other techniques. In general, MSNA burst/min is a
good indicator of sympathetic nerve activity 32-37. For example, direct measurement of
sympathetic nerve activity as reflected in MSNA has been a very useful tool to demonstrate
that increased sympathetic activity is an important factor in the pathogenesis of essential
hypertension 38-42. In chronic orthostatic intolerance, a syndrome of autonomic dysfunction
in young women MSNA have revealed an abnormal regional distribution of sympathetic activity
during orthostatic stress. 43, 44. Moreover, studies in children with complex regional
syndrome and adolescents have shown these patients reported systemic ANS symptoms including
dizziness, near syncope and postural tachycardia 45-49. Our case series of 5 complex regional
pain syndrome patients (4 male, 1 female, 32-51 years) with implanted epidural spinal cord
stimulator for pain relief 50 suggested that CRPS (Complex Regional Pain Syndrome) patients
have: 1) reduced vasoconstrictor response during Valsalva, 2) A greater blood pressure (BP)
drop during straining phase II as compared to normal and less blood pressure overshoot during
phase IV in CRPS patients with stimulator turned off and the BP response returns to normal
ranges during spinal stimulator turned on. Lastly, muscle sympathetic nerve activity improved
during SCS resulting in better blood pressure control. All these data suggest a tight
relationship between pain control and sympathetic function. As is well know, CVP is difficult
to treat because of its ill-defined nature and treatment with SCS has moderate success, but
predicting success in these difficult to treat patients will probably be increased by
correlating autonomic function; pain and therapy with spinal cord stimulation.
regional pain syndromes 1 , ischemic limb pain 2-5, failed back surgery syndrome 6, 7, and
refractory angina pectoris 8-11. Recently, Kapural et al. reported a case series of six
patients that underwent SCS for the treatment of chronic visceral pain (CVP)12, 13. SCS
reduced 50% of the patients' pain and improved patient functionality by 60% 14 . Animal
studies suggested that dorsal column pathways are involved in the transmission of visceral
pain 12, 13. Clinical studies in patients with visceral cancer have shown that interruption
of the fibers of the dorsal columns that ascend close to the midline of the spinal cord
significantly relieves pain and decreases analgesic requirement 15-18. Different studies
support the hypothesis that visceral pain perception is positively modulated by the
descending pathways from the medulla. Dorsal column lesion leads to a reduction of thalamic
activation by visceral stimuli and decreased visceral pain perception 19. Visceral
innervation occurs via sympathetic and parasympathetic pathways; parasympathetic afferents
enter the vagal afferents carrying nociceptive information enter trunks while sympathetic
afferents carrying nociceptive information enter at the levels T6 and L3. Therefore, limited
case series using SCS for CVP suggested that pain relief was achieved by blocking these
segments suppressing sympathetic outflow to the abdomen and pelvis 14. The relationship
between autonomic nervous system (ANS) and pain are poorly understood. Animal and clinical
research has provided evidence for close interaction between pain modulatory systems and the
ANS 20, 21. However, little is known about the ANS function in chronic pain patients. Our
previous funded work suggested that chronic low back pain (CLBP) patients have reduced LFRRI
(heart rate variability-low frequency) (not increased as expected) and that indices of the
vagal component of the Heart Rate Variability(HRV) (Root Mean Square of the Successive
Differences (RMSSD), heart rate variability-high frequency (HFRRI) were also attenuated. The
sympatho-vagal balance (LFRRI /HFRRI), a ratio of LF to HF which correlates with higher
sympathetic activation 22, was paradoxically increased 23. We previously demonstrated that
Low Frequency Systolic Blood Pressure (LFSBP) correlates with muscle sympathetic nerve
traffic during orthostatic load supported by a simplified model of blood pressure variability
24. We also showed that LFSBP can be abolished by ganglionic blockade demonstrating the
neurogenic origin of these oscillations in blood pressure 25. Additionally, our study
revealed decreased baroreflex indices (αHF and BRSLF) during sitting in CLBP patients. Blood
pressure was not different in CLBP patients, but there was a trend for higher heart rates
possibly caused by higher sympathetic activity to the heart. These findings of reduced
baroreflex sensitivity and changes in heart rate support hypothesized alterations in
cardio-vagal control in patients with chronic pain 26, 27. In summary, sympathetic function
has been assessed by indirect measures. There is no data available regarding the direct
assessment of sympathetic outflow in CVP patients. Sympathetic outflow is stimulus specific
28, 29. Therefore, the characterization of resting sympathetic outflow and stimulus-induced
sympathetic adjustments requires simultaneous measurements of activity by different
techniques. We propose using microneurography to assess the sympathetic function on a
second-to-second basis in CVP patients. Microneurography directly assess muscle sympathetic
nerve activity (MSNA). This technique is used to define sympathetic responses to a number of
standard physiologic maneuvers. It was first developed in Sweden by Wallin, who described the
technique for recording afferent muscle or skin sympathetic nerve activity 30, 31. MSNA
displays real-time sympathetic nerve activity, allowing definition of sympathetic responses
so transient that they would be lost to all other techniques. In general, MSNA burst/min is a
good indicator of sympathetic nerve activity 32-37. For example, direct measurement of
sympathetic nerve activity as reflected in MSNA has been a very useful tool to demonstrate
that increased sympathetic activity is an important factor in the pathogenesis of essential
hypertension 38-42. In chronic orthostatic intolerance, a syndrome of autonomic dysfunction
in young women MSNA have revealed an abnormal regional distribution of sympathetic activity
during orthostatic stress. 43, 44. Moreover, studies in children with complex regional
syndrome and adolescents have shown these patients reported systemic ANS symptoms including
dizziness, near syncope and postural tachycardia 45-49. Our case series of 5 complex regional
pain syndrome patients (4 male, 1 female, 32-51 years) with implanted epidural spinal cord
stimulator for pain relief 50 suggested that CRPS (Complex Regional Pain Syndrome) patients
have: 1) reduced vasoconstrictor response during Valsalva, 2) A greater blood pressure (BP)
drop during straining phase II as compared to normal and less blood pressure overshoot during
phase IV in CRPS patients with stimulator turned off and the BP response returns to normal
ranges during spinal stimulator turned on. Lastly, muscle sympathetic nerve activity improved
during SCS resulting in better blood pressure control. All these data suggest a tight
relationship between pain control and sympathetic function. As is well know, CVP is difficult
to treat because of its ill-defined nature and treatment with SCS has moderate success, but
predicting success in these difficult to treat patients will probably be increased by
correlating autonomic function; pain and therapy with spinal cord stimulation.
Inclusion Criteria:
- Chronic visceral pain patients candidates for spinal cord stimulation implant with no
other chronic diseases.
Exclusion Criteria:
- Diabetes, pulmonary or chronic cardiac diseases.
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