Chronic intrathecal cannulation enhances nociceptive responses in rats.

The influence of a chronically implanted spinal cannula on the nociceptive response induced by mechanical, chemical or thermal stimuli was evaluated. The hyperalgesia in response to mechanical stimulation induced by carrageenin or prostaglandin E2 (PGE2) was significantly increased in cannulated (Cn) rats, compared with naive (Nv) or sham-operated (Sh) rats. Only Cn animals presented an enhanced nociceptive response in the first phase of the formalin test when low doses were used (0.3 and 1%). The withdrawal latency to thermal stimulation of a paw inflamed by carrageenin was significantly reduced in Cn rats but not in Nv or Sh rats. In contrast to Nv and Sh rats, injection in Cn animals of a standard non-steroid anti-inflammatory drug, indomethacin, either intraperitoneally or into the spinal cord via an implanted cannula or by direct puncture of the intrathecal space significantly blocked the intensity of the hyperalgesia induced by PGE2. Cannulated animals treated with indomethacin also showed a significant inhibition of second phase formalin-induced paw flinches. Histopathological analysis of the spinal cord showed an increased frequency of mononuclear inflammatory cells in the Cn groups. Thus, the presence of a chronically implanted cannula seems to cause nociceptive spinal sensitization to mechanical, chemical and thermal stimulation, which can be blocked by indomethacin, thus suggesting that it may result from the spinal release of prostaglandins due to an ongoing mild inflammation.

[1]  A. Panerai,et al.  Interleukin‐1 and nociception in the rat , 1998, Journal of neuroscience research.

[2]  T. Yaksh,et al.  Cyclooxygenase inhibition and the spinal release of prostaglandin E2 and amino acids evoked by paw formalin injection: a microdialysis study in unanesthetized rats , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  A. Malmberg,et al.  The effect of morphine on formalin‐evoked behaviour and spinal release of excitatory amino acids and prostaglandin E2 using microdialysis in conscious rats , 1995, British journal of pharmacology.

[4]  A. Eschalier,et al.  A method to perform direct transcutaneous intrathecal injection in rats. , 1994, Journal of pharmacological and toxicological methods.

[5]  S. Ferreira,et al.  Glutamate spinal retrograde sensitization of primary sensory neurons associated with nociception , 1994, Neuropharmacology.

[6]  T. Yaksh,et al.  Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia. , 1994, The Journal of pharmacology and experimental therapeutics.

[7]  O. Hayaishi,et al.  Allodynia evoked by intrathecal administration of prostaglandin E2 to conscious mice , 1994, Pain.

[8]  A. Malmberg,et al.  Pharmacology of the Spinal Action of Ketorolac, Morphine, ST-91, U50488H, and L-PIA on the Formalin Test and an Isobolographic Analysis of the NSAID Interaction , 1993, Anesthesiology.

[9]  T. Yaksh,et al.  Effects of intrathecal strychnine and bicuculline on nerve compression-induced thermal hyperalgesia and selective antagonism by MK-801 , 1993, Pain.

[10]  Ronald Melzack,et al.  Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence , 1993, Pain.

[11]  A. Malmberg,et al.  Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. , 1992, The Journal of pharmacology and experimental therapeutics.

[12]  A. Malmberg,et al.  Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. , 1992, Science.

[13]  F. Porreca,et al.  The rat paw formalin test: comparison of noxious agents , 1990, Pain.

[14]  J. Holaday,et al.  Neurological dysfunction after intrathecal injection of dynorphin A (1-13) in the rat. I. Injection procedures modify pharmacological responses. , 1988, The Journal of pharmacology and experimental therapeutics.

[15]  R. Dubner,et al.  A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia , 1987, Pain.

[16]  M. Devor,et al.  Behavioural effects of receptor-specific substance P agonists , 1987, Pain.

[17]  T. Yaksh,et al.  Dynorphin A and related peptides administered intrathecally in the rat: a search for putative kappa opiate receptor activity. , 1986, The Journal of pharmacology and experimental therapeutics.

[18]  J. Levine,et al.  Indomethacin blocks central nociceptive effects of PGF2α , 1986, Brain Research.

[19]  K. Folkers,et al.  Intrathecal (D-Pro2, D-Trp7,9)-SP elicits hypoalgesia and motor blockade in the rat and antagonizes noxious responses induced by substance P. , 1982, Acta physiologica Scandinavica.

[20]  S. Ferreira Peripheral and central analgesia , 1981, PAIN.

[21]  S. Ferreira,et al.  Central and peripheral antialgesic action of aspirin-like drugs. , 1978, European journal of pharmacology.

[22]  S. Ferreira,et al.  The hyperalgesic effects of prostacyclin and prostaglandin E2. , 1978, Prostaglandins.

[23]  T. Yaksh,et al.  ANALGESIA MEDIATED BY A DIRECT SPINAL ACTION OF NARCOTICS , 1977 .

[24]  T. Yaksh,et al.  Chronic catheterization of the spinal subarachnoid space , 1976, Physiology & Behavior.

[25]  J. Shaw,et al.  Spontaneous and evoked release of prostaglandins from frog spinal cord. , 1966, The American journal of physiology.

[26]  M. Serpell,et al.  Intrathecal catheterization alone reduces autotomy after sciatic cryoneurolysis in the rat. , 1993, Life sciences.

[27]  J. Levine,et al.  Indomethacin blocks central nociceptive effects of PGF2 alpha. , 1986, Brain research.