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Thread: Neurontin and nerve regeneration - Dr. Young?

  1. #11
    Okay, I didn't mean to frighten anyone. I believe when I first came out of rehab I was on Bacoflen and heard that it suppresses regeneration but it wasn't a proven fact. I don't want to live in pain but I also don't want to inhibit spasms or regeneration which is why I checked with the expert. If Dr. Young has never heard this before then I will give the neurontin a try before I opt for an epidural or surgery.

    Deb

  2. #12
    Debbie7 i was one of the posters on that thread, i cant say my function has gotten any better since than. i would not be scared off from neurontin , and live with pain, neurontin gave me great pain relief, with a lot less side effects and quality of life and activities of daily living issues than narcotics.
    it extinguished the pain totally., and my pain was totally incapacitating, in higher doses it may cause bladder retention, but a lot of meds do, plus i was taking elavil too, which also causes bladder retention, it also affects my bowels quite a bit, but that could just be me..

  3. #13
    Banned Faye's Avatar
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    Originally posted by seneca:

    Dr. Young, some people have noticed an increase in sensation and motor control after reducing the dosage or stopping completely, same with baclofen. I don't think people believe that it stops or inhibits recovery but that it may cloak return because of the inhibitory effect it has on the CNS. It's a fairly potent sedative so isn't that to be expected?
    The same is true of valium. Rat studies have even proven that the use of valium reduces motor function return. Jason was on both baclofen and valium when he left the rehab.
    I wish we had known this and not agreed to taking these meds.
    These meds are routinely given to "make the patient more comfortable" and make caregiving easier in ER,ICU and rehab without any concern for possible negative consequences for neuron regeneration.

    It seems that two weeks after injury when most of the swelling subsides, chances are best for neuron regeneration, but obviously when sedated that opportunity may be lost for ever.

    PAIN does cause a huge problem, however instead of supressing the symptoms we need to find the cause to better treat it. We haven't found the right means to do this yet.

    "Together we stand, divided we fall..."

  4. #14
    Suspended Andy's Avatar
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    Who says Neurontin doesnt work? I'm still going through a ramping up on the dosage (I hope I dont have to get to the several gram plateau I hear about though), but doubling dosage yesterday resulted in much reduced neuro pain. I almost forgot what it was like to not have pins and needles over my lower half until yesterday. I'm not too concerned about masked recovery, as I doubt any of that will be happening to me.

  5. #15
    seneca,

    We should not mix drugs. So, let me discuss baclofen first. It is true that high doses of baclofen will produce muscle weakness and may reduce sensation. It does reduce spinal cord excitability and therefore will have both sensory and motor effects.

    Neurontin is different because it is an anti-epileptic drug. It should not have that much effect on normal motor and sensory function. As a drug for pain, it actually has remarkably few side-effects (for example, compared to opioids, tricyclic antidepressants, and other analgesics), even as very high doses.

    While suppression of neuronal activity may inhibit regeneration, and both neurontin and baclofen may do so at very high doses, I don't know any data that shows that either stops or inhibits regeneration.

    Wise.

  6. #16
    Originally posted by Wise Young:

    seneca,

    We should not mix drugs. So, let me discuss baclofen first. It is true that high doses of baclofen will produce muscle weakness and may reduce sensation. It does reduce spinal cord excitability and therefore will have both sensory and motor effects....

    While suppression of neuronal activity may inhibit regeneration, and both neurontin and baclofen may do so at very high doses, I don't know any data that shows that either stops or inhibits regeneration.

    Wise.
    Thanks Dr. Young, the reports regarding neurontin have been anecdotal.

    [This message was edited by seneca on 04-11-04 at 09:16 AM.]

  7. #17
    seneca, I am not sure that there is even anecodotal evidence for the claim. I don't think that I have heard anybody claiming that they have had less recovery after spinal cord injury if they have received neurontin or baclofen. I think that it is just a rumor.

    Several years ago, I remember that there was a discussion about the possibility that baclofen might inhibit regeneration. At that time, I looked hard for any published or anecdotal information concerning this possibility but don't think that I found any published papers on the subject.

    In http://www.vard.org/jour/01/38/6/mcdon386.htm there is an article in 2001 where the question was asked:
    Â*Â*There are also several testable hypotheses that would best be explored collaboratively. Could electrical stimulation be used in the sub-chronic time period to limit or prevent delayed apoptosis of oligodendrocytes? Will optimizing neural activity enhance regeneration? Do anti-spasmodic medications (e.g. baclofen) reduce neural activity and inhibit regeneration? Can electrical stimulation be used to modulate new cell birth and survival? Is activity below the level of the injury sub-optimal such that cell birth is reduced rendering adequate replacement of cells impossible, or is activity reduced such that cells are unable to migrate to or survive in the appropriate region? Can electric fields or electrical stimulation be used to modify guidance pathways or migration of cells? In constraint-induced forced use studies, for example, stroke patients who are made to use their impaired arm experience improved functional outcomes (37,38). However, in animal experiments if there is too much use too soon, the injury can be made worse (39,40). Do these results represent examples of the benefits of appropriately timed increased neural activity in the injured cortex? Can similar activity be used to enhance functional outcomes in SCI?
    Note that my laboratory studied GABA receptors on axons in the spinal cord. GABA depolarizes and reduces excitability of spinal axons. There are potential mechanisms by which baclofen may affect axonal growth but there is no evidence that it does so, either in an inhibitory or facilitory way.
    • Lee M, Sakatani K and Young W (1993). A role of GABAA receptors in hypoxia-induced conduction failure of neonatal rat spinal dorsal column axons. Brain Res. 601: 14-9. Department of Neurosurgery, New York University Medical Center, NY 10016. GABA (gamma-aminobutyric acid) depresses axonal conduction in neonatal dorsal columns. GABA released by injured spinal neurons may diffuse to white matter and contribute to secondary axonal damage. We studied the effects of hypoxia and GABAA receptor blockade on dorsal column conduction in vitro. The experiments compared the effects of hypoxia on longitudinally hemisected spinal cords and isolated neonatal dorsal columns. Before hypoxia, electrical stimulation elicited robust conducted compound action potentials in both isolated dorsal columns and hemicords. The tissues were superfused for 120 min with a hypoxic Ringer's solution saturated with 95% N2 and 5% CO2, followed by oxygenated Ringer's solution for 90 min. Isolated dorsal columns were remarkably insensitive to hypoxia. Response amplitudes fell by only 11 +/- 7% (n = 5) during hypoxia. In hemicords, however, hypoxia reduced response amplitudes by 56 +/- 16% (n = 5, mean +/- S.E.M.) and re-oxygenation did not restore response amplitude. We applied bicucullin (10(-5) M) to block GABAA receptors in the hemicords during hypoxia. Response amplitudes in bicucullin-treated hemicords fell by only 3 +/- 9% (n = 5) during hypoxia but declined 31 +/- 5% during re-oxygenation. These results suggest that endogenous GABA released from gray matter contributes to hypoxia-induced dorsal-column conduction failure.

    • Sakatani K, Chesler M, Hassan AZ, Lee M and Young W (1993). Non-synaptic modulation of dorsal column conduction by endogenous GABA in neonatal rat spinal cord. Brain Res. 622: 43-50. Department of Neurosurgery, New York University Medical Center, NY 10016. GABAA receptor activation can modulate axonal conduction in the isolated dorsal column of the neonatal rat spinal cord in vitro. However, it is not known whether axonal conduction in the dorsal column can be modulated by endogenous GABA in the developing spinal cord. We consequently compared the effects of GABA, a GABAA agonist, and a GABA uptake inhibitor on axonal conduction in the dorsal column of hemisected neonatal (0- to 9-day-old) rat spinal cords in vitro. Extracellular compound action potentials evoked by supramaximal stimuli were recorded at two points with glass microelectrodes. GABA (10(-4) to 10(-3) M) reversibly decreased the compound action potential amplitude and the population conduction velocity. At 10(-4) M, compound action potential amplitudes fell by 45.0 +/- 6.5% of control while the conduction velocity slowed by 11.8 +/- 4.3% (n = 5). The GABAA receptor agonist, isoguvacine, mimicked the effects of GABA on the dorsal column compound action potential. In contrast, while GABA at 10(-5) M decreased the amplitude by 7.7 +/- 3.1%, it increased conduction velocity by 9.7 +/- 1.3% (n = 5). The GABA uptake inhibitor, nipecotic acid (10(-3) M), consistently decreased the compound action potential amplitude by 17.7 +/- 6.5% (n = 6) but the conduction velocity slowed in four out of six preparations. In two instances, nipecotic acid decreased the amplitude and increased the conduction velocity. The effects of nipecotic acid on the dorsal column compound action potential were blocked in the presence of the GABAA antagonist bicuculline.(ABSTRACT TRUNCATED AT 250 WORDS).

    • Sakuma J, Ciporen J, Abrahams J and Young W (1996). Independent depressive mechanisms of GABA and (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide on young rat spinal axons. Neuroscience. 75: 927-38. Department of Neurosurgery, New York University Medical Center, NY 10016, USA. We compared the effect of GABA and the serotonin receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT) on compound action potential amplitudes, latency, and conduction velocity in the spinal cord isolated from young (eight to 13-day-old) Long-Evans hooded rats. Supramaximally activated conducting action potentials and extracellular K+ activity were recorded with microelectrodes from the cuneatus-gracilis fasciculi and corticospinal tract. In the cuneatus-gracilis fasciculi, 8-OH-DPAT (10(-4) M) significantly reduced response amplitudes by 26.1 +/- 10.3% (mean +/- S.D., P < 0.0001, paired t-test, n = 27) and increased latencies by 20.3 +/- 7.9% [P < 0.0001). GABA [10[-4) M) reduced/amplitudes by 31.7 +/- 15.0% [P < 0.0001, n = 28) and increased latencies by 6.1 +/- 5.4% [P < 0.0001). However, neither GABA nor 8-OH-DPAT significantly altered conduction velocities, suggesting that the latency shifts are due to changes in activation time and not conduction velocity. In cortical spinal tract, 8-OH-DPAT [10[-4) M) depressed response amplitudes by 18.9 +/- 9.6% [P < 0.05, n = 5), increased latencies by 23.3 +/- 7.2% [P < 0.0001), but reduced conduction velocities by 19.9 +/- 10.2%. GABA [10[-4) M) reduced amplitudes by 16.4 +/- 7.5% [P < 0.01, n = 5), increased latencies by 5.3 +/- 2.3% [P < 0.05), and did not change conduction velocities. Bicuculline or picrotoxin blocked the GABA effects but did not affect the 8-OH-DPAT effects on both tracts. The potassium channel blocker tetraethylammonium did not alter the 8-OH-DPAT effects. The Na+/K[+)-ATPase inhibitor ouabain [10[-6) M) markedly enhanced the depressive GABA effects from 27.9 +/- 12.0% to 49.4 +/- 24.5% [P < 0.01, n = 9), but had no effect on 8-OH-DPAT-mediated effects. These results suggest that GABA and serotonin agonists depress axonal excitability through different and independent mechanisms.

    • Saruhashi Y, Young W, Sugimori M, Abrahams J and Sakuma J (1997). Evidence for serotonin sensitivity of adult rat spinal axons: studies using randomized double pulse stimulation. Neuroscience. 80: 559-66. Department of Neurosurgery and Physiology, New York University Medical Center, NY 10016, U.S.A. We have recently shown both inhibitory and excitatory effects of serotonin on neonatal rat dorsal column axons. While neonatal rat dorsal column axons also respond to norepinephrine and GABA, adult rat dorsal columns are insensitive to the actions of both compounds. Therefore, we studied the effects of serotonin agonists on adult rat dorsal column axons using randomized double pulse stimuli at 0.2 Hz with random interpulse intervals of 3, 4, 5, 8, 10, 20, 30, 50 and 80 ms. The serotonin(1A) agonist, 8-hydroxy-dipropylaminotetralin-hydrobromide (8-OH-DPAT), significantly modulated test response amplitudes at 3, 4, 5 and 8 ms interpulse intervals by 29.6+/-4.0%, 17.4+/-2.1%, 9.6+/-2.3%, and 12.4+/-2.2% of conditioning pulse amplitudes, respectively. The mean latencies at 3, 4 and 5 ms interpulse intervals increased by 17.0+/-5.1%, 8.6+/-2.1%, and 5.1+/-1.4%, respectively (P<0.05). However, neither 10 microM 8-OH-DPAT nor 100 microM serotonin hydrochloride affected the compound action potentials evoked by conditioning or test pulses. In contrast, treatment with 100 microM quipazine dimaleate [a serotonin[2A) agonist) decreased the refractory period. While the response amplitudes to a 3-ms double pulse were reduced by 11.0+/-1.5% during the control period, the test response fell to only 2.4+/-1.8% of the conditioning response amplitudes after exposure to 100 microM quipazine. 8-OH-DPAT decreased the amplitude, prolonged the latency and increased the refractory periods of compound action potentials in the adult rat dorsal column, although a high concentration of the agonist [100 microM) was required for these effects. In contrast, the serotonin[2A) agonist, quipazine, decreased refractory periods. These results suggest that both serotonin[1A) and serotonin[2A) receptor subtypes are present on adult spinal dorsal column axons. Further, these receptors have opposing effects on axonal excitability, despite the fact that their sensitivities are relatively low.

    • Saruhashi Y, Young W, Sugimori M, Abrahams J and Sakuma J (1999). GABA increases refractoriness of adult rat dorsal column axons. Neuroscience. 94: 1207-12. Department of Neurosurgery, NYU Medical Center, New York, NY 10016, USA. We applied randomized double pulse stimulation for assessing the effects of GABA and a GABAA antagonist on compound action potentials in dorsal column axons isolated from adult rat. We stimulated the axons with double pulses at 0.2 Hz and randomly varied interpulse intervals between 3, 4, 5, 8, 10, 20, 30, 50 and 80 ms. Action potentials were measured using glass micropipettes. The first pulse was used to condition the response activated by the second test pulse. Concentrations of GABA of 1 mM, 100 microM and 10 microM did not affect action potential amplitudes or latencies activated by conditioning pulses. In the control studies, before drug administration, test pulses induced response amplitudes that were significantly decreased at 3-, 4- and 5-ms interpulse intervals. The test action potential amplitudes were 84.6 +/- 2.5%, 89.0 +/- 3.9% and 93.3 +/- 3.6% (mean +/- S.E.M.) of conditioning pulse levels, respectively. At 3-ms interpulse intervals, test response latencies were prolonged to 104.3 +/- 1.0%, but were unchanged at the other interpulse intervals. The 10 microM, 100 microM and 1 mM concentrations of GABA affected test response amplitudes. Application of 100 microM GABA reduced the amplitudes of test responses at 3-, 4-, 5- and 8-ms interpulse intervals, to 59.2 +/- 3.0%, 70.0 +/- 3.0%, 80.2 +/- 1.1% and 88.6 +/- 3.6% of the conditioning pulse amplitudes, respectively. At both 100 microM and 1 mM concentrations, GABA significantly prolonged the latencies of test responses. Treatment with 100 microM GABA prolonged the latencies of test responses at 3-, 4- and 5-ms interpulse intervals, to 119.3 +/- 3.1%, 107.3 +/- 2.8% and 105.5 +/- 2.5% of conditioning pulse latencies, respectively. The addition of 100 microM bicuculline methochloride, a GABAA antagonist, eliminated the effects of 100 microM GABA. The combined application of GABA and bicuculline (both 100 microM) did not affect amplitudes or latencies of test responses. These results suggest that GABA(A) receptor subtypes are present on the spinal dorsal column axons of adult rat, and that they modulate the excitability of the axons. The randomized double pulse methods reveal that GABA increases refractoriness of adult rat dorsal column axons.
    Wise.

    [This message was edited by Wise Young on 04-11-04 at 06:13 AM.]

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