No pain, no strain: Targin® mitigates pain and constipation following spinal cord injury.

BACKGROUND: Opioids effectively reduce chronic pain, but present significant side effects including opioid-induced constipation. Oxycodone/naloxone decreases pain and constipation in cancer patients, however its effect on spinal cord injury population remains understudied. METHODS: We assessed whether oxycodone/naloxone reduces pain, constipation, and severity of autonomic dysreflexia in an individual with spinal cord injury. A 55-year-old male with C5 lesion presented with chief complaint of chronic pain received 5/2.5 mg and 20/10 mg oxycodone/naloxone for 6 and 2 weeks, respectively. RESULTS: Oxycodone/naloxone improved pain, bowel function, and autonomic dysreflexia severity. INTERPRETATION: Oxycodone/naloxone was effective in managing chronic pain and constipation in the studied case.

Autonomic Dysreflexia as a Potential Adverse Effect of Duloxetine and Amitriptyline Combination Therapy: A Case Report.

Pharmacologic triggers of autonomic dysreflexia (AD) have rarely been described. This report describes the case of a 31-year-old woman with T3 American Spinal Injury Association Impairment Scale A spinal cord injury who developed recurrent AD while receiving duloxetine and amitriptyline combination therapy for neuropathic pain. After excluding other AD generators, duloxetine was discontinued and the AD episodes resolved. Although secondary hypertension is a known side effect of amitriptyline and duloxetine, neither drug has been previously associated with AD. One potential mechanism for inhibition of duloxetine metabolism is discussed. Unexplained AD in at-risk patients receiving duloxetine and amitriptyline should prompt consideration of an adverse reaction to combination therapy. LEVEL OF EVIDENCE: V.

[Subarachnoid hemorrhage due to autonomic dysreflexia: rare consequence of sexual stimulation in a paraplegic]. / Subarachnoidalblutung durch autonome Dysreflexie: Seltene Folge einer sexuellen Stimulation bei Paraplegie.

Nearly all men with spinal cord injury suffer from neurogenic sexual dysfunction which is often treated with phosphodiesterase-5 (PDE5) inhibitors. We describe a case of subarachnoid hemorrhage due to autonomic dysreflexia (AD) caused by sexual stimulation. Nitrates are frequently used for acute treatment of AD; however, the use of these drugs in combination with PDE5 inhibitors is contraindicated. Therefore, meticulous information from patients and relatives on the risk of AD and possible drug interactions is of vital importance.

Autonomic cardiovascular function and baroreflex sensitivity in patients with cervical dystonia receiving treatment with botulinum toxin type A.

OBJECTIVE: To investigate possible changes in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity in patients with primary cervical dystonia receiving chronic treatment with botulinum toxin type A. METHODS: Short-term power spectral analysis of heart rate and systolic blood pressure variability, high-frequency and low-frequency oscillations of heart rate variability, low frequency/high frequency ratio and baroreflex sensitivity (alpha index) were measured in 12 patients with cervical dystonia before and 2-4 weeks after botulinum toxin type A injection and compared with normative data. RESULTS: Before treatment, at rest, patients had significantly lower high frequency power than healthy subjects (p < 0.01), whereas no differences were found in low frequency power. Botulinum toxin injection in patients induced no changes in either power frequency. In patients before treatment and healthy subjects the low frequency oscillatory components increased similarly from rest to tilt (p < 0.01), but tilt induced lower low frequency values in patients than in healthy subjects (p < 0.01). In patients before treatment, the high frequency variations from rest to tilt remained unchanged, whereas in healthy subjects they decreased significantly (p < 0.01). Botulinum toxin type A injection in patients induced no changes in low frequency or high frequency powers. In patients before treatment the low frequency/high frequency ratio increased slightly from rest to tilt, but in healthy subjects increased significantly (p < 0.01). Botulinum toxin type A left the pretreatment low frequency/high frequency ratio unchanged. The alpha-index measured at rest in patients before treatment was lower than in healthy subjects (p<0.05), whereas during tilt was similar in both groups. The alpha-index measured after botulinum toxin injection in patients remained unchanged at rest and during tilt. CONCLUSIONS: Patients with cervical dystonia receiving treatment with botulinum toxin type A have mild, subclinical abnormalities in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity. These changes do not worsen after acute botulinum toxin type A injection.

Long-lasting hyperalgesia and sympathetic dysregulation after formalin injection into the rat hind paw.

Subcutaneous formalin injection has been used extensively to evaluate acute effects (over several hours) of chemical nociceptive stimulation on nociceptive reflexes. Also, a persistent hyperreflexia for mechanical and thermal stimulation, lasting 3 weeks after formalin injection, has been revealed and related to microglial activation in the spinal dorsal horn. The present study demonstrates more prolonged effects of formalin injection, lasting 6 weeks, on operant escape from nociceptive thermal stimulation. Operant escape requires cerebral processing of nociceptive input and can detect effects that are not limited to spinal or spinal-brain stem-spinal reflex circuits. Compared with rats injected with saline, escape responding to 44.5 degrees C and 47 degrees C stimulation was increased after bilateral s.c. injection of 5% formalin into the dorsal hind paws. The hyperalgesia outlasted visible signs of trauma (e.g. paw edema). Responses to 36 degrees C were not altered after formalin injection, providing a control for effects of the peripheral injury on activity levels or exploratory tendencies. Skin temperature recordings from the forepaws and contralateral hind paw during 44.5 degrees C stimulation of the left hind paw provided an indirect measure of cutaneous blood flow in formalin- and saline-injected animals. Normal reductions in skin temperature during thermal stimulation were attenuated (nearly eliminated) at 1 and 2 weeks after formalin injection and partially recovered by 10 weeks. Thus, formalin-induced tissue injury produced a long-term secondary hyperalgesia, accompanied by a reduced sympathetic responsivity. The similar time-course for these phenomena suggests that there are mechanistic linkages between focal injury, autonomic dysregulation and enhanced pain sensitivity.

Diminished skin vasodilator response to local heating in patients with long-standingsubacute myelo-optico-neuropathy.

BACKGROUND: Local heating of non-glabrous skin increases skin blood flow (SkBF) in two phases: the initial peak (P1) is mediated by sensory axon reflex, and the plateau phase (P2) is thought to be mediated by local production of substances including nitric oxide. We evaluated P1 and P2 responses in subacute myelo-optico-neuropathy (SMON). METHODS: SkBF response to local heating from 32 degrees C (5 min of baseline) to 42 degrees C (at least for 30 min) of the dorsal surface of the hand skin were measured in 7 SMON patients (67.6+/-10.0 years) and 7 normal control volunteers (65.0+/-7.4 years) participated. RESULTS: Mean values of SkBF at P1 (SkBFP1) and SkBF during P2 (SkBFP2) were significantly lower in SMON patients than in controls (p<0.05, p<0.05). Mean SkBFP1/SkBF at baseline (SkBFbase) and SkBFP2/SkBFbase ratios were significantly lower in SMON patients than in controls (p<0.01 and p<0.05, respectively). CONCLUSIONS: The SkBF response to local heating was diminished in SMON patients. This may reflect the involvement of the spinal cord, peripheral sensory nerves, and sympathetic post-ganglionic nerves in SMON.

Corticotropin-releasing factor modulates cardiovascular and pupillary autonomic reflexes in man: is there a link to inflammation-induced autonomic nervous hyperreflexia?

In two recent studies, we found autonomic nervous hyperreflexia in subjects with chronic inflammatory diseases, particularly, in those subjects with higher degrees of systemic inflammation. Since corticotropin-releasing factor (CRF) is induced by inflammatory stimuli and acts within the brain to change neuroendocrine and autonomic activity, we investigated CRF modulation of standard autonomic nervous reflexes. Fifteen healthy subjects were administered 100 microg CRF i.v., which led to a short-term increase of heart rate (p < 0.001) and a decrease in systolic and diastolic blood pressure (p < 0.050). These changes were accompanied by a reduction in heart rate variation at rest (p = 0.010) and during the respiratory sinus arrhythmia test (p = 0.019), and a reduction of pupillary latency time (p = 0.038). In further 21 normal subjects we studied the effect of prednisolone treatment on autonomic nervous function (100 mg/d during three days --> CRF reduction), which resulted in an increase of heart rate (p < 0.001), increase of heart rate variation during the respiratory sinus arrhythmia test (p < 0.001), increase in pupillary latency time (p = 0.012), a increase in maximal pupillary area (p = 0.002), and a decrease in diastolic blood pressure (p = 0.002). In conclusion, induction of a low central CRF content by prednisolone leads to a marked hyperreflexia in respiratory sinus arrhythmia and hyporeflexia in the latency time test. It is obvious that CRF can regulate autonomic reflexes. Possibly, central CRF status may also influence autonomic reflexes during chronic inflammation due to chronically changed central CRF concentration.