The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury.

We performed a double-blinded, randomized, controlled trial in 15 patients to determine the efficacy of intrathecal morphine or clonidine, alone or combined, in the treatment of neuropathic pain after spinal cord injury. The combination of morphine and clonidine produced significantly more pain relief than placebo 4 h after administration; either morphine or clonidine alone did not produce as much pain relief. In addition, lumbar and cervical cerebrospinal fluid (CSF) concentrations, sampled at these levels at different times after administration were examined for a relationship between pain relief and CSF drug concentration. Lumbar CSF drug concentrations were initially several orders of magnitude larger than those in cervical CSF. After 1-2 h, the concentrations of morphine in cervical CSF markedly exceeded those of clonidine. The concentration of morphine in the cervical CSF and the degree of pain relief correlated significantly. We conclude that intrathecal administration of a mixture of clonidine and morphine is more effective than either drug administered alone and is related to the CSF-borne drug concentration above the level of spinal cord injury. If there is pathology that may restrict CSF flow, consideration should be given to intrathecal administration above the level of spinal cord damage to provide an adequate drug concentration in this region.

Neuropathic pain in the perioperative period.

The presence of neuropathic pain in the postoperative period may be associated with unnecessary suffering, particularly if the diagnosis is not made and treatment modalities chosen are ineffective. It is likely that inadequate management of acute pain may set the scene for progression to a chronic pain state. The underlying neurobiological mechanisms whereby short-term stimuli may lead to long-term plasticity and structural changes in the nociceptive pathways are now being unraveled. The possibility arises that acute, intensive intervention may avoid or significantly reduce the development of these changes and subsequent chronic pain. Early diagnosis and treatment becomes a priority. There is a need for further research in this area to determine whether or not such theoretical potential can be turned to therapeutic advantage.

Intrathecal clonidine and baclofen in the management of spasticity and neuropathic pain following spinal cord injury: a case study.

Spasticity and pain are common disabling sequelae following spinal cord injury (SCI) and are often difficult to manage. The two problems are also not infrequently related. A variety of pharmacological and other approaches have been described for management of these problems in SCI. This case study reports a 32-year-old woman with an established incomplete C5 tetraplegia (anterior cord syndrome) who developed severe, intractable anal spasm following a hemorrhoidectomy, which persisted despite very good healing. This prevented evacuation of her bowels and resulted in severe rectal pain and episodes of autonomic dysreflexia. Attempts to modify the rate and mode of delivery of intrathecal baclofen through an existing programmable infusion pump failed to reduce anal sphincter spasm or improve symptoms. A right-sided pudendal block with lignocaine provided some relief. Clonidine was added to baclofen in the pump reservoir and both drugs were administered intrathecally in combination. This resulted in an immediate improvement in anal sphincter spasm and pain relief, allowing rapid reestablishment of her normal bowel pattern without need for any supplemental analgesia. It appears that intrathecal clonidine may have an important role in the treatment of spasticity, either as a single or an adjuvant agent, when intrathecal baclofen alone is ineffective or there is increasing tolerance to baclofen. Intrathecal clonidine may also prove useful in the management of intractable neuropathic pain.

Neural blockade in chronic pain.

Neuroblockade techniques can serve many functions in the management of the chronic pain patient. These various functions are discussed and a brief insight given for their use in specific pain syndromes. A run-down of the type of blocks useful in the management of cancer pain is also given.

The induction of specific proteases for insulin-like growth factor-binding proteins following major heart surgery.

Insulin-like growth factors (IGF-I and IGF-II) circulate bound to specific high-affinity binding proteins (IGFBPs). Recent evidence has shown that in pregnancy and severe illness, specific proteases modify these binding proteins, reducing their affinity for IGFs. We have studied 12 patients, undergoing elective coronary artery vein-bypass graft surgery, for the appearance of these proteases and have demonstrated the induction of two independent, heat-labile, cation-dependent proteases. Proteolytic activity directed against IGFBP-3 was detected in all patients between 24 h and 5 days after surgery; the second IGFBP-4 specific protease was active 1 h after sternotomy. The total IGF-I levels were found to decrease following surgery, with the IGF-I distribution in the plasma being radically altered from that seen prior to the operation. One day after the operation the majority of the IGF-I, instead of being bound in the relatively inert 150 kDa complex, was associated with the smaller binding proteins which are more readily accessible to the tissues. These findings are in contrast to pregnancy where, despite similar proteases, the majority of the IGF-I remains in the 150 kDa complex. The alteration seen in IGF-I distribution after surgery did not appear to be a direct result of the IGFBP-3 proteolytic activity or an effect of the addition of heparin to the circulation. The potential increase in bioavailability of IGFs caused by the alteration in carrier protein may play a pivotal role in countering the catabolic state induced by surgery.

Rapid progression of tracheal stenosis associated with tracheopathia osteo-chondroplastica.

Tracheopathia osteochondroplastica (TPO) is a rare, but increasingly recognised condition in which there is accumulation of calcium phosphate with benign submucous proliferation of cartilage and bone beneath the tracheal mucosa, often with squamous metaplasia of the mucosal columnar epithelium. This condition is usually asymptomatic, but may be slowly progressive, causing haemoptysis, dry cough and dyspnoea. We report a case of TPO in which there was rapid progression of tracheal stenosis such that the size of endotracheal tube that the upper airway would accept changed from 8.00 mm to 3.0 mm during a six-week period. This extreme reduction in airway calibre had not been detected on spirometry nine days prior to his final admission. This is the first report of such rapid progression of tracheal stenosis associated with TPO.