Epidural morphine in the treatment of chronic pain.
Treatment of chronic pain is far from satisfactory. Although a number of modes of treatment are available none are without drawbacks. Recently morphine receptors have been identified in various areas of brain and substantia gelatinosa of the spinal cord. Since drugs injected in epidural space can reach spinal cord, epidural injection of morphine may produce relief of pain. We have reported earlier the effect of epidural morphine in patients with acute and chronic pain.
This study presents detailed findings regarding the efficacy of 2 mg morphine injected in the epidural space in patients with severe chronic pain.
The study was carried out in two parts: (1) Open study and (2) Double blind study. Sixteen patients participated in the single blind study and 8 in the double blind study. Informed consent was obtained from all the patients.
Details of the patients are given in [Table 1] and [Table 2].
Patients with peripheral vascular disease (PVD) were (angiographically proved) of the distal type, i.e. involving blood vessels below femoral due to smoker's arteritis. All these patients were grade III of Boyd's classification i.e. with rest pain. Detailed neurological examination was carried out to rule out any other associated factor contributing to pain. All these patients had previously received conventional treatment consisting of:
(1) Sedatives and analgesics-Analgin 500 mg tds, diazepam 10 mg at night. (2) Vasodilators-Xanthinol nicotinate 150-300 mg tds.
(3) I.V. Lomodex-500 ml per day for 5 consecutive days.
(4) Antibiotics-Injection Dicrysticin when required. (Pr. Penicillin, 3 lac; tryst. Penicillin 1 lac units and Streptomycin 1 gm.).
(5) Local treatment such as excision of gangrene and wound dressing.
All the patients were taking sedatives and analgesics as the sleep was disturbed due to rest pain.
Other patients had chronic pelvic pain or backache due to varying etiology [Table 1], which restricted their normal activity confining them to bed. One patient with perineal tear had straight leg raising test positive (pain at 40°). The test was repeated after epidural morphine.
(1) Relief of rest pain-graded as percentage relief of pain from initial pain.
(2) Analgesic and sedative consumption.
(3) Resumption of normal activity. The assessment was by the surgical colleague.
Group I (Open study) : These patients were given 2 mg morphine (Preservative free) diluted in 10 ml normal saline in the epidural space at L3-L4 in sitting position. Patients maintained sitting posture for half an hour following the epidural injection. Group II (Double blind study) : These patients were given 2 mg morphine (4 cases) in 10 ml saline or 10 ml normal saline alone (4 cases) in random order in the epidural space at L3-L4
Neither the patient nor the person assessing pain (surgeon) was aware of the identity of the drug.
Results are given in Tables 1 and 2. All the patients who were given epidural morphine (From Study I and Study II) volunteered 100% relief of pain with onset within 2 minutes of epidural injection and peak effect in 10 minutes. They did not require any analgesics or sedatives for sleep.
In the patient with perineal tear the leg could be raised to 70° without pain and physiotherapy was possible. The other patients had 100% relief of pain, they were ambulatory and did not require analgesics or sedatives.
The analgesic effect lasted for 2 to 21 days [Table 1].
None of the patients had loss of other sensations or muscle paralysis. There was no fall in blood pressure or change in pulse rate. None of the patients had any euphoric symptoms but 6 of the PVD patients had a crying spell within 5 minutes of the injection which lasted for less than 2 minutes. Three patients did not pass urine for 12 hours.
In 4 patients given epidural normal saline, there was 10-20% relief of pain which lasted for 3-4 hours. None of the patients could resume normal activity and all required analgesics and sedatives in the same doses as before epidural injection and none had crying spells.
This study shows that a small dose (2 mg) of morphine given in epidural space produces remarkable relief of pain lasting for 2-3 weeks in patients with chronic pain. Normal saline injected epidurally produced 10-20% relief of pain lasting for 3-4 hours. The analgesia produced by epidural morphine is not accompanied by loss of other sensations or change in blood pressure and pulse rate.
Although none of the patients had any euphoric symptoms, 6 patients had crying spell immediately after relief of pain. Whether this was due to sudden relief of pain or the effect of morphine on the central nervous system, is difficult to judge.
The onset of action of epidural morphine was within 2 minutes as opposed to 5-10 minutes for the onset of action following epidural local anaesthetic. Rapid penetration of epidural local anaesthetic agent into cerebrospinal fluid has been demonstrated. The spread of epidurally administered morphine has however not been reported. It has been postulated that the longitudinal spread in epidural space leads to leakage through intervertebral foramina, diffusion through dural root sleeves (ink cuff areas), diffusion across perineurium and leakage by vascular absorption. Behar et al have suggested that epidural morphine probably acts on substantia gelatinosa of the spinal cord. An extradural site of action, however, cannot be excluded particularly in the light of the fact that methenkephalin has been identified in peripheral nerves. Whatever be the effect on nerves it is reversible because the patients have had recurrence of pain after two to three weeks. Efficacy of subarachnoid morphine has been reported.
This work was supported by KEM Hospital Research Society grant, which is gratefully acknowledged.