The article of Brill and colleagues  published close to 25 yr since the beginning of such an important period in the history of anaesthesia as the use of spinal opiates for selective spinal analgesia in the treatment of pain, is well timed. I wish to congratulate both the Editor of the European Journal of Anaesthesiology and the authors for the selection of this topic.
Of special interest in this article, were the early citations concerning the intrathecal introduction of morphine for the relief of pain, around 1900, by physicians from Romania and Japan. These isolated reports happened long before knowledge of the role of the dorsal horn opioid receptors and their ligands in the control of pain transmission. However, the widespread use of opioids by the spinal route for pain relief in human beings, started only after the intensive development of spinal cord neurophysiology and knowledge about its contribution to pain modulation in laboratory animals.
The administration of spinal morphine in human beings was not actually reported first from Israel, as written in the paper by Brill and colleagues. Morphine was injected by Wang and colleagues from the Mayo Clinic, via the intrathecal route, in patients suffering from malignancy and their results were reported in 1979 in Anaesthesiology . Soon thereafter, in 1979, the group of anaesthesiologists from Israel reported the effects of morphine by the epidural approach, in patients with various acute and chronic pain conditions . It is to be expected, of course, that more than one group would be investigating aspects of intrathecal and epidural opioid analgesia at the same time. Cousin and colleagues used epidural meperidine and published their first results in 1979  and not in 1984 as quoted by Brill and colleagues. To my knowledge during the year 1979, intrathecal morphine was also under investigation in Paris by physicians from the Department of Anaesthesiology of Dr. Viars. Their results were published at a later date and included plasma kinetic studies of spinal morphine .
The central analgesic effect of the epidural approach was confirmed from the very beginning by the finding that small doses of morphine  or meperidine  administered extradurally reached their specific dorsal horn receptors.
The importance of the first publications, in addition to the encouraging clinical results, was to stimulate the in-depth pharmacokinetic studies which followed and thus to form the basis for the understanding of the advantages and limitations of this novel method of pain treatment and its correct implementation in the clinical setting.
Department of Anesthesiology; Hadassah University Hospital; Jerusalem, Israel
1. Brill S, Gurmann GM, Fisher A. A history of neuraxial administration of local analgesics and opioids. Eur J Anaesthesiol
2. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology
3. Behar M, Magora F, Olshwang D, Davidson JT. Epidural morphine in the treatment of pain. Lancet
4. Cousin MJ, Maher LE, Glynn CJ, Wilson PR, Graham JR. Selective spinal analgesia. Lancet
5. Chauvin M, Samii K, Schermann JM, Sandouk P, Bourdon R, Viars P. Plasma pharmacokinetics of morphine after I. M. extradural and intrathecal administration. Br J Anaesth
6. Magora F, Olshwang D, Eimerl D, et al.
Observations on extradural morphine analgesia in various pain conditions. Br J Anaesth