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Scheer, et al. (2005). Reduced sleep efficiency in cervical spinal cord injury; association with abolished night time melatonin secretion.

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    Scheer, et al. (2005). Reduced sleep efficiency in cervical spinal cord injury; association with abolished night time melatonin secretion.

    People with spinal cord injury often have trouble sleeping. It has also long been known that people with spinal cord injury often have low melatonin, a hormone that plays a role in determining the diurnal (day-night) cycles. The authors now report that low melatonin leads to sleeping disturbances in people with cervical spinal cord injuries. Control subjects with thoracic spinal cord injury did not differ from non-injured controls. However, those people with cervical spinal cord injury took longer to reach REM sleep (a stage of sleep indicative of deep sleep), i.e. 220 minutes compared to 34 minutes in subjects with thoracic spinal cord injury.

    [*] Scheer FA, Zeitzer JM, Ayas NT, Brown R, Czeisler CA and Shea SA (2005). Reduced sleep efficiency in cervical spinal cord injury; association with abolished night time melatonin secretion. Spinal Cord Study design:Case-controlled preliminary observational study.Objective:Melatonin is usually secreted only at night and may influence sleep. We previously found that complete cervical spinal cord injury (SCI) interrupts the neural pathway required for melatonin secretion. Thus, we investigated whether the absence of night time melatonin in cervical SCI leads to sleep disturbances.Setting:General Clinical Research Center, Brigham & Women's Hospital, Boston, USA.Methods:In an ancillary analysis of data collected in a prior study, we assessed the sleep patterns of three subjects with cervical SCI plus absence of nocturnal melatonin (SCI levels: C4A, C6A, C6/7A) and two control patients with thoracic SCI plus normal melatonin rhythms (SCI levels: T4A, T5A). We also compared those results to the sleep patterns of 10 healthy control subjects.Results:The subjects with cervical SCI had significantly lower sleep efficiency (median 83%) than the control subjects with thoracic SCI (93%). The sleep efficiency of subjects with thoracic SCI was not different from that of healthy control subjects (94%). There was no difference in the proportion of the different sleep stages, although there was a significantly increased REM-onset latency in subjects with cervical SCI (220 min) as compared to subjects with thoracic SCI (34 min). The diminished sleep in cervical SCI was not associated with sleep apnea or medication use.Conclusion:We found that cervical SCI is associated with decreased sleep quality. A larger study is required to confirm these findings. If confirmed, the absence of night time melatonin in cervical SCI may help explain their sleep disturbances, raising the possibility that melatonin replacement therapy could help normalize sleep in this group.Sponsorship:This work was supported by the NIH (GCRC Grant M01-RR-02635 and Grant HL-64815). Dr Ayas is supported by the BCLA, CIHR, and MSFHR.Spinal Cord advance online publication, 30 August 2005; doi:10.1038/ 1Harvard Medical School and Division of Sleep Medicine, Brigham and Women's Hospital, Boston, USA.

    The diminished sleep in cervical SCI was not associated with sleep apnea or medication use.
    Wow - we cervical SCIs get a double whammy. First there's the very high incidence of sleep apnea (my hunch is that many cervical SCIs have it and are unaware of the source of their fatigue), and now low melatonin levels. What do we have to do to get a good night's sleep!

    I've been a C5/C6 complete quad since I was 7 (I am 30 now). At 18 I had a spinal fusion to correct the significant scoliosis that is often (always?) associated with infant SCI, and during the two procedures my right lung had to be collapsed (and I think my diaphragm had to be cut in half and re-stitched - my memory is a little fuzzy). I noticed fatigue starting about 6 months later, although I don't know if it was related to the fusion surgery, an age thing, or pure co-incidence. At 29 I finally had a sleep study upon the insistence of a good friend who's an endocrinologist that has done some research into sleep disorders.

    My diagnosis? 127 apneas an hour on average! CPAP has changed my life like you wouldn't believe. My energy levels are through the roof, I've lost around 30 kgs (66 lbs) now that I have the energy to diet and exercise, and I'm more excited about my 30s than I ever was about my 20s. I think the effect of poor sleep on a cervical SCI cannot be overstated.

    Have you ever seen a human heart? It looks like a fist wrapped in blood! Larry in 'Closer', a play by Partick Marber


      Here I read this and figuring it's just another BS study...

      ..consisting of flawed testing, and/or coincidental results.

      Then again, here I am writing this after midnight, cuz I cannot fall asleep dammit


        Last edited by NWC4; 20 Sep 2005, 8:43 PM.


          Originally posted by Wise Young
          Control subjects with thoracic spinal cord injury did not differ from non-injured controls. However, those people with cervical spinal cord injury took longer to reach REM sleep (a stage of sleep indicative of deep sleep), i.e. 220 minutes compared to 34 minutes in subjects with thoracic spinal cord injury.
          LOL no WONDER my dad is always tired!!! Nurses are in a MINIMUM of every two hours, day or night, so he probably never actually even reaches REM.


          Fear Less... Hope More...
          Whine Less... Breathe More...
          Talk Less... Say More...
          Hate Less... Love More...
          And All Good Things Are Yours.


            Wow. And here I was thinking my reduced sleeping time was due to reduced energy use.

            For the months I was vent-free at night, I did get a poorer quality of rest.

            Since 83% was the median for cervical SCIs, I wonder what the mean was? Given that there were only three cervical injuries studied, I would bet that the C4 (if vent-free) scored lower than 83%, the C6 scored 83%, and the C6/7 scored higher than 83%.

            More details would definitely be helpful.
  's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.


              Here are some additional studies on the subject of sleep and melatonin in people with spinal cord injury:
              1. Norrbrink Budh C, Hultling C and Lundeberg T (2005). Quality of sleep in individuals with spinal cord injury: a comparison between patients with and without pain. Spinal Cord. 43: 85-95. Spinalis SCI unit, Karolinska University Hospital, Stockholm, Sweden. STUDY DESIGN: A cross-sectional descriptive study of self-reported quality of sleep in individuals with a spinal cord injury (SCI). OBJECTIVES: To assess and describe subjective quality of sleep in patients with SCI, with and without pain. SETTING: Spinalis SCI unit, Stockholm, Sweden. METHODS: A total of 230 patients with an SCI were mailed a questionnaire containing queries about pain intensities, pain unpleasantness, mood, and sleep quality (Basic Nordic Sleep Questionnaire) to assess quality of sleep in patients with SCI with and without pain. RESULTS: Of the 192 questionnaires that were returned (response rate 83.4%), 191 were analysed. Patients were divided into three groups: (1) those who reported no pain (n=50), (2) those who reported intermittent pain (n=42), and (3) those who suffered from continuous pain (n=99). Patients suffering from continuous pain rated pain intensity and unpleasantness significantly higher than those who only suffered from intermittent pain. The group with continuous pain also reported the poorest quality of sleep and the highest ratings of anxiety and depression of the three groups. Anxiety, together with pain intensity and depression, were the main predictors for poor sleep quality. CONCLUSIONS: Poor subjective sleep quality was associated with higher ratings of pain intensity, anxiety, and depression. It is possible that melatonin serves as a modulator of these different aspects.
              2. Li Y, Jiang DH, Wang ML, Jiao DR and Pang SF (1989). Rhythms of serum melatonin in patients with spinal lesions at the cervical, thoracic or lumbar region. Clin Endocrinol (Oxf) 30: 47-56. The neural pathway essential for the diurnal rhythm of serum melatonin was studied in humans. Blood samples from 17 patients with chronic lesions of cervical (n = 8), low thoracic or lumbar (n = 9) spinal cord were collected at 0200, 0400, 1000 and 1400 h of their normal light-dark cycle. Blood samples were also collected from eight control subjects at 0200 and 1400 h. No special treatment of food, drug or photoperiod was implemented. Serum melatonin was extracted by dichloromethane and determined by radioimmunoassay. In patients with cervical spinal lesions (C3-C7), it was found that serum melatonin levels were low and no diurnal rhythm was observed. Conversely, diurnal rhythm of circulating melatonin with significantly higher levels (P less than 0.01) in the dark period were observed in individuals with injuries at the low thoracic or lumbar regions (T9-L2). In the second experiment, blood samples from two other patients were collected for three consecutive days during acute period of spinal injuries (cervical or upper thoracic region) and serum melatonin concentrations were determined. Again, there were low levels of serum melatonin with no observable diurnal rhythm in the patient with cervical lesion (C4-5). However, diurnal rhythms were maintained with high levels in the dark period in the patient with upper thoracic spinal (T2-3) transection. Our data suggest that the cervical region of the spinal cord is part of the neural pathway essential for the diurnal rhythm of pineal melatonin secretion in human beings. Department of Physiology, University of Hong Kong.
              3. Kneisley LW, Moskowitz MA and Lynch HG (1978). Cervical spinal cord lesions disrupt the rhythm in human melatonin excretion. J Neural Transm Suppl 311-23. To determine whether spinal cord lesions disrupt the diurnal activity of the human pineal, urinary melatonin levels were measured over 24 hours (4 or 8-hourly intervals) in male patients with clinical evidence of cervical spinal cord transection. During the waking state, levels of melatonin in these subjects ranged from 3.2--13.5 ng/4 hours; during sleep and darkness, values ranged from 1.8--10.5 ng/4 hours. Levels of serum cortisol, aldosterone, and growth hormone showed rhythmic variations in these subjects. The absence of significant nocturnal melatonin increases distinguishes quadriplegic subjects from normal males and from one subject with a lesion of the lumbar spinal cord. These differences may be caused by "decentralization" of the pineal organ due to a lesion within the cervical spinal cord interrupting descending sympathetic fibers. If so, the human pineal, like that of other mammals, is regulated, at least in part, by activity within the central nervous system via sympathetic nervous connections.

              Melatonin is also potentially important as a treatment of acute spinal cord injury.
              1. Zeitzer JM, Ayas NT, Shea SA, Brown R and Czeisler CA (2000). Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia. J Clin Endocrinol Metab 85: 2189-96. The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion. Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
              2. Genovese T, Mazzon E, Muia C, Bramanti P, De Sarro A and Cuzzocrea S (2005). Attenuation in the evolution of experimental spinal cord trauma by treatment with melatonin. J Pineal Res. 38: 198-208. Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy. Melatonin is the principal secretory product of the pineal gland and its role as an immuno-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. In the present study, we evaluated the effect of melatonin treatment, in a model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 50 g) to the dura via a four-level T5-T8 laminectomy. SCI in rats resulted in severe trauma characterized by edema, neutrophil infiltration and apoptosis (measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling staining). Infiltration of spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for nitrotyrosine and Poly(ADP-ribose) (PAR) in the spinal cord tissue. In contrast, the degree of (a) spinal cord inflammation and tissue injury (histological score), (b) nitrotyrosine and PAR formation, (c) neutrophils infiltration and (d) apoptosis was markedly reduced in spinal cord tissue obtained from rats treated with melatonin (50 mg/kg i.p., 30 min before SCI, 30 min, 6 hr, 12 hr and 24 hr after SCI). In a separate set of experiment we have clearly demonstrated that melatonin treatment significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that treatment with melatonin reduces the development of inflammation and tissue injury events associated with spinal cord trauma.
              3. Cayli SR, Kocak A, Yilmaz U, Tekiner A, Erbil M, Ozturk C, Batcioglu K and Yologlu S (2004). Effect of combined treatment with melatonin and methylprednisolone on neurological recovery after experimental spinal cord injury. Eur Spine J. 13: 724-32. Department of Neurosurgery, Inonu University Medical Faculty, PK 230, Malatya, Turkey. Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Methylprednisolone (MP), by reducing edema and protecting the cell membrane against peroxidation, is the only pharmacological agent with a proven clinically beneficial effect on SCI. Melatonin, known as a free radical scavenger, has been shown to have an effect on lipid peroxidation following experimental SCI. The purpose of this study was to examine the effect of MP and melatonin on neurological, ultrastructural, and electrophysiological recovery. Female albino rats weighing 200-250 g were randomized into five groups of 18 rats each and six rats for the control group. Weight-drop trauma was performed for each group and a 30-mg/kg single dose of MP for rats in group 1, a 10-mg/kg single dose of melatonin for rats in group 2, and MP and melatonin in the same doses for rats in group 3 were administered immediately after trauma. The rats in group 4 were the vehicle group (treated with ethanol) and group 5 was the trauma group. The motor and somatosensory evoked potentials were recorded at the 4th hour, the 24th hour, and on the 10th day of the study for six rats in each group. Posttraumatic neurological recovery was recorded for 10 days using "motor function score" and inclined plane test. After electrophysiological study the rats were terminated for an analysis of lipid peroxidation level of the injured site of the spinal cord. Electron microscopic studies were performed to determine the effects of melatonin, MP, and the combined treatment with MP and melatonin on axons, neurons, myelin, nucleus, and intracytoplasmic edema. The groups treated with MP, melatonin, and a combination of both had significantly enhanced electrophysiological, biochemical, and neurological recovery and also showed better ultrastructural findings than the trauma and vehicle groups. Although combined treatment was significantly more effective on lipid peroxidation than melatonin or MP treatments alone, at the 10th day, neurobehavioral, electrophysiological, and ultrastructural recovery were at the same level. In conclusion, MP, melatonin, and MP and melatonin combined treatment modalities improved functional recovery at the same level. Future studies involving different doses of melatonin and different dose combinations with MP could promise better results since each drug has a different anti-oxidative mechanism of action.
              4. Erten SF, Kocak A, Ozdemir I, Aydemir S, Colak A and Reeder BS (2003). Protective effect of melatonin on experimental spinal cord ischemia. Spinal Cord. 41: 533-8. Department of Neurosurgery, Faculty of Medicine, Inonu University, Malatya, Turkey. STUDY DESIGN: Experimental animal model to assess ischemic spinal cord injury following occlusion of the thoraco-abdominal aorta. OBJECTIVES: To measure whether melatonin administered to rabbits before and after occlusion exerts an effect on the repair of ischemia-reperfusion (IR) injury. SETTING: Medical Biology Laboratory, Inonu University, Malatya, Turkey. METHODS: Rabbits were divided into three IR treatment groups and one sham-operated (ShOp) control group. The three treatment groups had their infrarenal aorta temporarily occluded for 25 min, while the ShOp group had laparotomy without aortic occlusion. Melatonin was administered either 10 min before aortic occlusion or 10 min after the clamp was removed. Physiologic saline was administered to the control animals. After treatment, the animals were euthanized and lumbosacral spinal cord tissue was removed for the determination of relevant enzyme activities. RESULTS: Malondialdehyde levels, indicating the extent of lipid peroxidation, were found to be significantly increased in the nonmelatonin treated (IR) group when compared to the ShOp group. Melatonin, whether given to pre- or post occlusion groups, suppressed malondialdehyde levels below that of the ShOp group. Catalase (CAT) and glutathione peroxidase (GSH-Px) enzyme activities were increased in the IR group compared to the ShOp group. Melatonin given preocclusion resulted in a significant decrease in both CAT and GSH-Px enzyme levels. The superoxide dismutase (SOD) enzyme activity was decreased in the ischemia-reperfusion treatment group. However, the melatonin treatment increased SOD enzyme activity to levels approximating that of the ShOp group. CONCLUSION: To our knowledge, this is the first study that shows the effects of melatonin administered both pre- and postischemia on induced oxidative damage to injured spinal cords. Our data also expands on reports that melatonin administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.
              5. Topsakal C, Kilic N, Ozveren F, Akdemir I, Kaplan M, Tiftikci M and Gursu F (2003). Effects of prostaglandin E1, melatonin, and oxytetracycline on lipid peroxidation, antioxidant defense system, paraoxonase (PON1) activities, and homocysteine levels in an animal model of spinal cord injury. Spine 28: 1643-52. STUDY DESIGN: Investigation of the effects of prostaglandin E1, melatonin, and oxytetracycline on lipid peroxidation, antioxidant and paraoxonase activities, and homocysteine levels in an experimental model of spinal cord injury. OBJECTIVES: To determine the antioxidant efficacy of prostaglandin E1, melatonin, and oxytetracycline and whether paraoxonase and homocysteine can be used as monitoring parameters in the acute oxidative stress of spinal cord injury. SUMMARY OF BACKGROUND DATA: Melatonin has been found useful in spinal cord injury in previous studies. No study exists investigating the effects of melatonin, prostaglandin E1, and oxytetracycline as well as the response type of paraoxonase enzyme and homocysteine levels in the acute oxidative stress of spinal cord injury. METHODS: Sixty-three male albino Wistar rats were anesthetized with 400 mg/kg chloral hydrate and divided into 5 groups. The G1 (n = 7) control group provided the baseline levels. G2-G5 underwent T3-T6 total laminectomies and spinal cord injuries by clip compression at the T4-T5 levels. Medications were applied to G3-G5 right after clip compression. Hence, G2 constituted laminectomy + injury, G3 laminectomy + injury + prostaglandin E1; G4 laminectomy + injury + melatonin, and G5 laminectomy + injury + oxytetracycline groups. Animals were decapitated either the first or fourth hour after injury. Spinal cord tissue and blood malonyldialdehyde and plasma homocysteine levels, plasma glutathione peroxidase, superoxide dismutase, paraoxonase activities were assayed. The SPSS 9.0 program was used for statistical analysis and graphics. Intergroup comparisons were made by Bonferroni corrected Mann Whitney U test (P < 0.025) and intragroups comparisons by Wilcoxon Rank test (P < 0.03). RESULTS: In injury groups, plasma homocysteine levels decreased and paraoxonase activities increased as erythrocyte superoxide dismutase levels and plasma glutathione peroxidase activities decreased in parallel to increases of tissue and blood malonyldialdehyde levels. These alterations were relatively suppressed by prostaglandin E1, melatonin, and oxytetracycline administrations in varying degrees. Melatonin was the most powerful agent, particularly at the fourth hour. Oxytetracycline was also effective, both at the first and fourth hour. Prostaglandin E1 was effective in comparison to injury group, but not as much as melatonin and oxytetracycline. CONCLUSIONS: Melatonin and oxytetracycline are effective in preventing lipid peroxidation in spinal cord injury. Paraoxonase and homocysteine can be used in monitoring the antioxidant defense system as well as superoxide dismutase and plasma glutathione peroxidase, both in injury and medicated groups. Department of Neurosurgery, Firat University School of Medicine, Elazig, Turkey.
              6. Kaptanoglu E, Tuncel M, Palaoglu S, Konan A, Demirpence E and Kilinc K (2000). Comparison of the effects of melatonin and methylprednisolone in experimental spinal cord injury. J Neurosurg 93: 77-84. OBJECT: Melatonin is a very effective antioxidant agent. This study was performed to investigate the effects of melatonin in experimental spinal cord injury (SCI). The authors also compared its effects with those of methylprednisolone, which also protects the spinal cord from secondary injury because of its antioxidant effect on membrane lipids. METHODS: Adult male albino rats were used for the study, and paraplegia was produced using a previously described weight-drop technique. Melatonin and methylprednisolone were given intraperitoneally by bolus injections of 100 mg/kg and 30 mg/kg, respectively, immediately after induction of trauma. The animals were killed, and 1-cm samples of injured spinal cord were obtained at 1, 24, and 48 hours postinjury. Lipid peroxidation was estimated by thiobarbituric acid test. Electron microscopic studies were performed to determine the effects of melatonin on neurons, axons, and subcellular organelles after experimental SCI. A grading system was used for quantitative evaluation. Following SCI, there was significant increase in lipid peroxidation. In melatonin- and methylprednisolone-treated groups, lipid peroxidation was found to decrease to the baseline (preinjury) levels. There was a significant difference between trauma-alone and treatment groups, but no statistical difference was found between the melatonin- and methylprednisolone-treated groups. Electron microscopic findings showed that SCI produced by the weight-drop technique resulted in profound tissue damage. CONCLUSIONS: Both melatonin and methylprednisolone have been shown to protect neuron, axon, myelin, and intracellular organelles including mitochondrion and nucleus. However, this study provides quantitative evidence that this protection of neurons and subcellular organelles of spinal cord after secondary injury is much more obvious in melatonin-treated rats than those treated with methylprednisolone. In view of these data, melatonin has been shown to be very effective in protecting the injured spinal cord from secondary injury. Department of Neurosurgery, Ankara Numune Hospital, Turkey.
              7. Fujimoto T, Nakamura T, Ikeda T and Takagi K (2000). Potent protective effects of melatonin on experimental spinal cord injury. Spine 25: 769-75. STUDY DESIGN: Experimental biochemical, behavioral, and histologic investigations of spinal cord injury in rats. OBJECTIVE: To investigate the effects of melatonin, a pineal hormone, in compression ischemic-induced spinal cord injury. SUMMARY OF BACKGROUND DATA: The implication of activated neutrophils in the worsening of spinal cord injury has been shown. Melatonin was shown to play an important role in protecting animal cells from neutrophil-induced toxicity and damage by free radicals. There is no report on using melatonin for spinal cord injury. METHODS: Spinal cord injury was induced by placing 25 g of weight extradurally on the rat spinal cord at T12 for 20 minutes. The rats were randomly divided into three groups. Sham rats had only laminectomy. Melatonin rats were injected with melatonin (2.5 mg/kg) intraperitoneally (intraperitoneal) five times: at 5 minutes, then 1, 2, 3, and 4 hours after the injury. Correspondingly, the control rats were injected with saline. Measured levels of lipid peroxidation estimated thiobarbituric acid reactive substances (TBARS) and the accumulation of leukocytes at the site of trauma, which were evaluated by measuring tissue myeloperoxidase activity. The recovery was assessed by using three clinical scoring systems, and histologic changes of the damaged spinal cord were examined. RESULTS: The thiobarbituric acid reactive substances content in the spinal cord increased after the injury, with two peaks (at 1 and 4 hours), and nitrogen mustard-induced leukocytopenia significantly attenuated the thiobarbituric acid reactive substances content in four 4 after injury. Also in these 4 hours, myeloperoxidase activity increased and melatonin injection reduced thiobarbituric acid reactive substances content and myeloperoxidase activity, which attenuated the motor deficits as well. Histologic findings showed that the melatonin group had less cavity formation than the control group. CONCLUSION: Results showed that injection of melatonin reduced thiobarbituric acid reactive substances content and myeloperoxidase activity, facilitating recovery of the damaged spinal cord. Department of Orthopedic Surgery, Kumamoto University School of Medicine, Kumamoto, Japan.

              Melatonin may also be potentially helpful for neuropathic pain
              1. Tu Y, Sun RQ and Willis WD (2004). Effects of intrathecal injections of melatonin analogs on capsaicin-induced secondary mechanical allodynia and hyperalgesia in rats. Pain. 109: 340-50. Department of Anatomy and Neurosciences, Marine Biomedical Institute, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1069, USA. Melatonin, its agonists/antagonists were administered intrathecally (i.t.) before/after intradermal injection of capsaicin. Capsaicin produced an increase in the paw withdrawal frequency (PWF) in the presumed area of secondary mechanical allodynia and hyperalgesia. Melatonin agonists in the absence of a capsaicin injection decreased the PWF significantly, whereas melatonin antagonists given intrathecally alone were ineffective in the absence of a capsaicin injection. Pre-treatment with a melatonin agonist i.t. caused a reduction in the PWF after capsaicin. In contrast, the PWF increased after capsaicin with pre-administration of a melatonin antagonist i.t. Combined pre-treatment with melatonin and a melatonin antagonist i.t. prevented the change in PWF induced by melatonin alone after capsaicin. Intrathecal post-treatment with a melatonin agonist reduced the enhanced PWF that followed an injection of capsaicin, but treatment with a combination of a melatonin agonist and its antagonist did not alter the responses. The PWF was unaffected when melatonin analogs were applied i.t. at the T6 level or were injected intramuscularly adjacent to the L4 vertebra. In spinal rats, the data showed comparable effects of melatonin analogs on capsaicin-induced secondary mechanical hyperalgesia. Animal motor function tested by 'activity box' showed that motion activity was not affected by i.t. melatonin or its antagonist. These results suggest that activation of the endogenous melatonin system in the spinal cord can reduce the generation, development and maintenance of central sensitization, with a resultant inhibition of capsaicin-induced secondary mechanical allodynia and hyperalgesia.
              2. Ulugol A, Dokmeci D, Guray G, Sapolyo N, Ozyigit F and Tamer M (2005). Antihyperalgesic, but not antiallodynic, effect of melatonin in nerve-injured neuropathic mice: Possible involvements of the l-arginine-NO pathway and opioid system. Life Sci The present study was undertaken to determine the effects of intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) melatonin on mechanical allodynia and thermal hyperalgesia in mice with partial tight ligation of the sciatic nerve, and how the nitric oxide (NO) precursor l-arginine and the opiate antagonist naloxone influence this effect. A plantar analgesic meter was used to assess thermal hyperalgesia, and nerve injury-induced mechanical hyperalgesia was assessed with von Frey filaments. 1-5 weeks following the surgery, marked mechanical allodynia and thermal hyperalgesia developed in neuropathic mice. Intracerebroventricular and intraperitoneal melatonin, with its higher doses, produced a blockade of thermal hyperalgesia, but not mechanical allodynia. Administration of both l-arginine and naloxone, at doses which produced no effect on their own, partially reversed antihyperalgesic effect of melatonin. These results suggest that although it has different effects on neuropathic pain-related behaviors, melatonin may have clinical utility in neuropathic pain therapy in the future. It is also concluded that l-arginine-NO pathway and opioidergic system are involved in the antihyperalgesic effect of melatonin in nerve-injured mice. Department of Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey.
              Last edited by Wise Young; 21 Sep 2005, 12:12 AM.


                I've been using melatonin for about 7 years. It really makes me groggy. 3mg at bedtime. C5 29 years post.
                Who are these time beings? And, why are we always doing things for them?

                If it wasn't for C, we'd be using BASI, PASAL and OBOL.


                  From an MSN article I read this morning...

                  How to improve your sleep
                  • Eat a light snack before bedtime to help produce serotonin (the calming hormone). Try a light snack — 200 calories or less — that’s mainly carbohydrate with a touch of protein. Many scientists claim that by combining an ample dose of carbohydrate together with a small amount of protein (which contains the amino acid tryptophan) your brain produces serotonin, which is known as the “calming hormone.” And when we’re calm, we are certainly more apt to fall asleep.
                  Suggested bedtime snacks:
                  1 slice of whole wheat toast topped with 1 small slice of low-fat cheese
                  1/2 cup healthy cereal topped with 1/2 cup skim milk
                  1 banana with 1 teaspoon of peanut butter
                  1 rice cake topped with 1 tomato slice and 1 slice turkey breast

                  • Regular exercise can increase your odds of getting a good night’s sleep. But avoid exercise within three hours of going to bed, as this will boost alertness and have a negative effect on sleep. Studies have shown that exercising more than three to six hours before going to bed has the most positive effect on falling asleep and staying asleep.
                  Sleep aid supplements
                  • <LI class=textBodyBlack>Melatonin has gotten a great deal of attention in the past few years because this hormone controls the body’s circadian rhythm — our internal 24-hour clock that tells us when to sleep and when to wake up. As we get older, we produce less melatonin, which may account in part for insomnia in older adults. I would not recommend supplemental doses without speaking with your physician first. Studies have not been conclusive in regard to its effectiveness, and these supplements may interact with other medications.
                  • Valerian root is an herb believed to have a calming, relaxing effect on the body. It has been used for centuries to treat insomnia, mild anxiety and restlessness. The exact mechanism of action is unknown. However, it may act as a depressant to the central nervous system to produce a mild tranquilizing effect. As with melatonin supplements, first speak with your personal physician to find out if it’s an appropriate option — and certainly first try the other sleep inducers discussed above.

                  Fear Less... Hope More...
                  Whine Less... Breathe More...
                  Talk Less... Say More...
                  Hate Less... Love More...
                  And All Good Things Are Yours.


                    This is interesting. I thought I was becoming nocturnal.

                    Welcome to The Flat Earth Society


                      my mom was trying to convince me to tell my doc that i can't sleep but i always said no. i hate taking more than i need to, and i definitely didn't want a sleep med. she mentioned melatonin supplements but i'm still wary because i don't feel fatigued from lack of sleep. the strange thing is, i never had a problem sleeping till recently, and my injury happened a year ago, although i am c6-7 incomplete.
                      Never take life seriously, nobody gets out alive anyway

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                        Originally posted by slowtuna
                        I've been using melatonin for about 7 years. It really makes me groggy. 3mg at bedtime. C5 29 years post.
                        c-5 28 yrs post injury I take neurtion valium baclofen & morphine by pump still have that nasty nerve pain does melatonin help with pain?


                          My 78 y.o. Dad has a C-5 injury from Jan 15. 2006. He is suffering from extreme lethargy during the day and generally seems REALLY out of it a lot of the time. I was starting to suspect sleep apnea but now I wonder if this could be it. He is supposed to be transferred to a VA hospital next week. I guess they could test for this when he gets there?

                          Wise, can you think of anything else that would cause him to become so extrememly tired most of the day, lose most short term memory, and become very confused at times? (He's been like this much more since being off the vent about 2 weeks ago.) And I don't see think anything in his list of meds that would cause it.


                            thank you dr.wise for posting so many amaizing things about sci .
                            you help us a lot to fight sci.
                            god bless you.


                              Melatonin works for me!

                              I take two .3mg tablets before bed. I'm C6 almost 8 years post injury and I've been using melatonin for the past year.