Alternative Intrathecal Agents for the Treatment of Pain

There is a need to develop alternative agents for intrathecal pain therapy for patients who either cannot tolerate the side effects of or who no longer obtain sufficient analgesia with opioids. The experimental use of several compounds in intrathecal drug delivery is currently in progress, with the development of clonidine as the single most important advance in the improvement of pain treatment. Clonidine, an α2‐adrenergic receptor agonist, appears to be safe and effective in the treatment of cancer and nonmalignant pain, with its effects most pronounced in patients whose pain consists of a neuropathic component. Other possible effective agents for intrathecal delivery include bupivacaine, octreotide, and SNX‐111. The preclinical and clinical profiles for these promising new intrathecal pain medications are discussed.

[1]  A. Rauss,et al.  Meta-analysis of the efficacy of extradural clonidine to relieve postoperative pain: an impossible task. , 1998, British journal of anaesthesia.

[2]  I. Curelaru,et al.  Continuous Intrathecal Infusion of Opioid and Bupivacaine in the Treatment of Refractory Pain Due to Postherpetic Neuralgia: A Case Report , 1998, Neuromodulation : journal of the International Neuromodulation Society.

[3]  R. Luther,et al.  Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium channel blocker, in the management of intractable brachial plexus avulsion pain. , 1997, The Clinical journal of pain.

[4]  R. Luther,et al.  Sympatholysis after neuron-specific, N-type, voltage-sensitive calcium channel blockade: first demonstration of N-channel function in humans. , 1997, Journal of cardiovascular pharmacology.

[5]  R. Portenoy,et al.  Clinical realities and economic considerations: special therapeutic issues in intrathecal therapy--tolerance and addiction. , 1997, Journal of pain and symptom management.

[6]  J. Paice,et al.  Clinical realities and economic considerations: efficacy of intrathecal pain therapy. , 1997, Journal of pain and symptom management.

[7]  K. Omote,et al.  Antinociceptive Interaction of Intrathecal α2‐adrenergic Agonists, Tizanidine and Clonidine, with Lidocaine in Rats , 1997, Anesthesiology.

[8]  R. Luther,et al.  Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX-111, produces spinal antinociception in rat models of acute, persistent and neuropathic pain. , 1996, The Journal of pharmacology and experimental therapeutics.

[9]  J. Eisenach.  Three Novel Spinal Analgesics: Clonidine, Neostigmine, Amitriptyline , 1996, Regional Anesthesia & Pain Medicine.

[10]  W. Winkelmüller,et al.  Long-term effects of continuous intrathecal opioid treatment in chronic pain of nonmalignant etiology. , 1996, Journal of neurosurgery.

[11]  T. Guo,et al.  Dexmedetomidine Injection into the Locus Ceruleus Produces Antinociception , 1996, Anesthesiology.

[12]  R. Penn,et al.  Intrathecal Clonidine and Tizanidine in Conscious Dogs: Comparison of Analgesic and Hemodynamic Effects , 1996, Anesthesia and analgesia.

[13]  I. Curelaru,et al.  Continuous Intracisternal and High Cervical Intrathecal Bupivacaine Analgesia in Refractory Head and Neck Pain , 1996, Anesthesiology.

[14]  R. Penn,et al.  Intraspinal morphine for chronic pain: a retrospective, multicenter study. , 1996, Journal of pain and symptom management.

[15]  P. Hardy,et al.  Long-term Use of Subarachnoid Clonidine for Analgesia in Refractory Reflex Sympathetic Dystrophy , 1995, Regional anesthesia and pain medicine.

[16]  J. Eisenach,et al.  Epidural clonidine analgesia for intractable cancer pain , 1995, Pain.

[17]  A. Malmberg,et al.  Effect of continuous intrathecal infusion of ω-conopeptides, N-type calcium-channel blockers, on behavior and antinociception in the formalin and hot-plate tests in rats , 1995, Pain.

[18]  S. Rutkowski,et al.  Intrathecal morphine and clonidine in the management of spinal cord injury pain: a case report , 1994, Pain.

[19]  Y. Olsson,et al.  Intrathecal and epidural somatostatin for patients with cancer. Analgesic effects and postmortem neuropathologic investigations of spinal cord and nerve roots. , 1994 .

[20]  T. Yaksh,et al.  Voltage-sensitive calcium channels in spinal nociceptive processing: blockade of N- and P-type channels inhibits formalin-induced nociception , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  J. Bianchi,et al.  Epidural administration of liposome-associated bupivacaine for the management of postsurgical pain: a first study. , 1994, Journal of clinical anesthesia.

[22]  H. Wulf,et al.  The stability of mixtures of morphine hydrochloride, bupivacaine hydrochloride, and clonidine hydrochloride in portable pump reservoirs for the management of chronic pain syndromes. , 1994, Journal of Pain and Symptom Management.

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

[24]  J. Eisenach,et al.  Epidural Clonidine Treatment for Refractory Reflex Sympathetic Dystrophy , 1993, Anesthesiology.

[25]  R. Lanning,et al.  Intrathecal infusional analgesia for nonmalignant pain: analgesic efficacy of intrathecal opioid with or without bupivacaine. , 1993, Journal of pain and symptom management.

[26]  Z. Wiesenfeld‐Hallin,et al.  The differential effects of morphine and the alpha 2-adrenoceptor agonists clonidine and dexmedetomidine on the prevention and treatment of experimental neuropathic pain. , 1993, Anesthesia and analgesia.

[27]  O. Patroni,et al.  Dose-Related Hemodynamic and Analgesic Effects of Intrathecal Clonidine Administered after Cesarean Section , 1993, Regional Anesthesia & Pain Medicine.

[28]  H. Benameur,et al.  Toxicity of bupivacaine encapsulated into liposomes and injected intravenously: comparison with plain solutions. , 1993, Anesthesia and analgesia.

[29]  H. Turndorf,et al.  Prolongation of spinal anesthesia. Differential action of a lipid drug carrier on tetracaine, lidocaine, and procaine. , 1992, Anesthesiology.

[30]  R. Penn,et al.  Octreotide: a potent new non-opiate analgesic for intrathecal infusion , 1992, Pain.

[31]  Z. Wiesenfeld‐Hallin,et al.  Intrathecal administration of clonidine suppresses autotomy, a behavioral sign of chronic pain in rats after sciatic nerve section , 1991, Neuroscience Letters.

[32]  S. Hassenbusch,et al.  Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. , 1991, Neurosurgery.

[33]  S. Einarsson,et al.  Long‐term intrathecal morphine and bupivacaine in “refractory” cancer pain. I. Results from the first series of 52 patients , 1991, Acta anaesthesiologica Scandinavica.

[34]  L. Conrad,et al.  Subarachnoid bupivacaine analgesia for seven months for a patient with a spinal cord tumor. , 1990, Anesthesiology.

[35]  L. Linder,et al.  Epidural versus intrathecal morphine-bupivacaine: assessment of consecutive treatments in advanced cancer pain. , 1990, Journal of pain and symptom management.

[36]  C. Post,et al.  Local Anesthetics Potentiate Spinal Morphine Antinociception , 1988, Anesthesia and analgesia.

[37]  R. Moore,et al.  ROLE OF SPINAL NORADRENERGIC SYSTEM IN TRANSMISSION OF PAIN IN PATIENTS WITH SPINAL CORD INJURY , 1986, The Lancet.

[38]  R. Saunders,et al.  Continuous intrathecal hydromorphone and clonidine for intractable cancer pain. , 1986, Journal of neurosurgery.

[39]  S. Savage,et al.  Intrathecal morphine tolerance: use of intrathecal clonidine, DADLE, and intraventricular morphine. , 1985, Anesthesiology.

[40]  L. Jenkins,et al.  Epidural blockade for cesarean section comparing lidocaine hydrocarbonate and lidocaine hydrochloride. , 1985, Anesthesiology.

[41]  N. Rawal.  Spinal antinociception: clinical aspects. , 1995, Annals of medicine.

[42]  S. Cooper,et al.  Anesthetic activity of the lipospheres bupivacaine delivery system in the rat. , 1992, Anesthesia progress.

[43]  S. Benita,et al.  Spinal anesthesia: significant prolongation of the pharmacologic effect of tetracaine with lipid solution of the agent. , 1991, Anesthesiology.