Biochemistry of pain relief with intracerebral stimulation. Few facts and many hypotheses.

On the basis of data obtained from subprimates subjected to acute pain stimuli, it has been hypothesized that the suppression of chronic pain in man during stimulation in the periventricular region involves endogenous opioid mechanisms. However, there is at present no direct and unequivocal proof that the pain relief in man is necessarily and entirely dependent upon such mechanisms. There exist several putative substances with opiate-like properties but they are difficult to identify. The assay methods lack specificity and cross-reactions are common. There are only a few studies published on the influence of intracerebral stimulation in man on the CSF-content of opioid substances; the changes observed are inconsistent, and data are only given on patients having satisfactory pain relief. Furthermore, measurements have been made only during the course of a few hours and nothing is reported on the relationship between the changing concentrations of the substance and the level of pain. The observation that Naloxone may reverse the effect of intracerebral stimulation has become the keystone in postulating common mechanisms for stimulation-produced pain relief and morphine analgesia. The fact, that Naloxone is sometime ineffective or has to be used in huge, and unphysiological, doses is generally disregarded. There are a number of substances which may serve as neurotransmittors in pain transmission and pain inhibition but their mode of action in the generation and suppression of chronic pain is entirely unknown. Data collected from various European clinics covering more than 200 patients subjected to intracerebral stimulation show that the outcome of this treatment is highly unpredictable. Intracerebral stimulation as a clinically useful treatment of chronic pain can not be further developed unless hard data on its biochemical background in man are provided.

The effect of patient age, gender, and tibial component fixation on pain relief after cementless total knee arthroplasty.

Cementless total knee arthroplasties (TKAs) were prospectively evaluated for pain relief in 1110 knees. The effect of screws in the tibial component, the age of the patients, and the gender of the patients were studied to determine the effect of these parameters on pain relief one and two years postsurgery. The group with screws in the tibial component (Ortholoc II) had a significantly higher percentage of pain-free knees at one year than at two years postsurgery, and the older patients had a significantly higher rate of pain-free knees at one- and two years postsurgery than the younger patients. Older female patients with Ortholoc I TKAs had a significantly higher percentage of pain-free knees than did older male patients at one-year postsurgery, but not at two years. The group with screws in the tibial components (Ortholoc II) had a higher percentage of pain-free knees at one-year postsurgery than did the Ortholoc I knees, but there was no difference between Ortholoc I and II at two-years postsurgery. In the Ortholoc II group, there was also no difference in results among sexes or between patients older and younger than 65 years old. The correlation coefficient was calculated to evaluate the relationship between body weight and the degree of pain after TKA. No significant correlation could be found at one and two years after surgery.

An integrated pain relief service for labour: co-operation between obstetricians, anaesthetists and midwives.

Epidural injections were performed by obstetricians on 1012 patients in a pain relief service in which there was clinical co-operation between anaesthetists and obstetricians. A consultant anaesthetist collaborated in the training of staff providing the service. Midwives maintained the epidural analgesia with top-up doses as part of their traditional role in providing pain relief in labour. Eight-eight per cent of patients were fully satisfied, 10% were helped and 2% had failed epidurals. The forceps rate was 30% and the dural tap rate 1.4%. Junior obstetric staff in training grades can with adequate safeguards make a significant contribution to running an obstetric epidural service.

Test instrument for predicting the effect of rigid braces in cases with low back pain.

The difficulty of predicting the acceptance and the result of wearing rigid braces has been identified before and is reported in the literature. Therefore a test instrument has been developed and tested. The intention is that the test instrument can imitate a rigid brace. Furthermore, different attributes of the rigid brace can be altered. Thus the range of the lordosis, the level of maximal dorsal support and the amount of abdominal support can be altered. By changing these parameters the maximal pain relief is sought. A good correlation between the result in the test instrument and the rigid brace manufactured according to the information from the former was seen (93%). No false negative results were seen. Thus, if no acceptance or pain relief was seen in the test instrument no pain relief could be expected in a rigid brace. Another purpose of this test instrument is to simplify the manufacture of the brace and to transfer easily the information gained from the test instrument to the brace with the aid of a so called measuring device.

Brain stimulation.

Electrical stimulation in the PAG has been shown to elicit profound analgesia in experimental animals that is at least in part due to the release of endogenous opioid substances. Electrical stimulation in the thalamic nuclei VPL and VPM inhibits the activation of spinal dorsal horn neurons by noxious stimuli. Acute electrical stimulation in these two targets relieves chronic pain in about 80% of patients. Chronic electrical stimulation by permanently implanted electrodes relieves pain in about 70% of patients with pain of peripheral or nociceptive origin but in only about 50% of patients with central pain resulting from deafferentation. Stimulating electrodes are implanted stereotactically by a burr hole under local anesthesia. Transient complications occur in 15% to 25% of patients and include infections, malfunctions of the stimulating hardware, pain at the implant sites, and mild temporary neurologic deficits. Permanent complications, including hemiparesis, intracranial hemorrhage, and death, occur in 1% to 2% of patients. Brain stimulation is recommended for the treatment of chronic pain in patients in whom other forms of treatment have failed. The technique is reasonably safe and provides pain relief for a group of patients who have exhausted all other therapeutic modalities. Unfortunately, not all patients receive effective pain relief with brain stimulation. Other stimulation targets such as the K-F nucleus in the parabrachial region of the brain stem are currently being explored in an attempt to provide pain relief to a greater proportion of patients. In addition, improvements in stimulation hardware have made the technique easier and more effective.

Egg membrane as a new biological dressing in split-thickness skin graft donor sites: a preliminary clinical evaluation.

BACKGROUND: This preliminary investigation attempted to determine the effectiveness of egg membranes as a new biological dressing to promote infection-free healing and provide pain relief over split-thickness skin graft (STSG) donor sites. METHODS: Eighteen patients, with 28 STSG donor sites who were admitted to the LinKou Burn Center from August 1997 to July 1999, were selected for this trial. The bilateral thighs were the main donor sites for STSG. To compare different dressings, Surgilon, B.G.C. (beta-glucan collagen), and Biobrane were applied to the same donor sites, and epithelialization, pain relief, fluid accumulation, hematoma formation, and the occurrence of rejection or infection were monitored post-application. RESULTS: The average wound healing time with egg membrane application was 11.64 +/- 1.29 (range, 10 to 13) days. Meanwhile, the average wound healing times for B.G.C. (6 patients) and Biobrane (6 patients) were 14.5 +/- 0.84 and 14.0 +/- 0.63 days, respectively. Finally, Surgilon (16 patients) had the longest healing time, at 16 +/- 1.41 days. On average, complete pain relief was achieved by 7.3 +/- 0.70 days for egg membrane application, while for B.G.C., Biobrane, and Surgilon, complete pain relief occurred by 7.0 +/- 0.89, 6.0 +/- 0.63, and 10.0 +/- 0.37 days, respectively. Finally, no infection or rejection developed during healing. CONCLUSIONS: From this preliminary study, egg membrane may be an ideal STSG donor site dressing, as it possesses properties of pain relief, wound protection, promotion of healing, and low cost. However, the limited unit size must be overcome, and its clinical application for burn wounds should be studied.

Radiotherapy for pain relief in locally recurrent colorectal cancer.

Eighteen patients with local recurrence of colorectal cancer have been treated by external beam radiotherapy for pain relief. Seven received a fractionated course of 4500cGy and the remainder received single fractions of 1000cGy, a number being treated more than once. The median survival for all patients once recurrence had produced pain was 7 months. Treatment benefit was recorded in 71% treated by fractionated courses and in 66% by single fractions. The duration of pain relief was 3 months for each method. The repeatability of single fraction treatment indicates that this is a worthwhile alternative technique, particularly for those in poor general condition.

Differences in midwives' approaches to pain relief in labour.

OBJECTIVE: To examine the influence of midwives' approaches on the care given to women for pain relief during labour. DESIGN: Non-participant observation was used to collect data on midwives' behaviours during interactions with women in labour. SETTING: A large teaching hospital in Northern Ireland. PARTICIPANTS: Observations focused on interactions that were related to pain relief and involved 11 midwives caring for 15 women throughout the first stage of labour. KEY FINDINGS: Midwives' approaches to pain relief differed; at one extreme the midwife acted as 'a cold professional' whilst at the other extreme she was observed to be 'a disorganised carer'. In the middle of these two extremes was the 'warm professional'; her approach had a positive influence on the women's experience of labour pain. IMPLICATION FOR RESEARCH: Further research is needed to develop a profile of the factors that 'make' for a warm professional. The information gained could be used to teach midwives the skills of being 'a warm professional', in particular, the value of effective communication for sensitive care such as pain relief in labour.

Start of oral morphine to cancer patients: effective serum morphine concentrations and contribution from morphine-6-glucuronide to the analgesia produced by morphine.

OBJECTIVE: To investigate the serum concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) and the relationships between serum concentrations and clinical effects associated with start of morphine treatment in cancer patients. METHODS: Forty patients with malignant disease and intolerable pain on weak opioids (codeine/dextropropoxyphen) were included. After a wash-out period, titration with immediate-release (IR) morphine was started. When a stable dose was achieved, the morphine treatment was changed to slow-release (SR) morphine in equivalent daily dosages. Clinical data and serum concentrations of morphine, M3G and M6G were obtained at the end of the IR and SR morphine treatment periods. RESULTS: The mean trough serum morphine concentration associated with pain relief was 66 nmol/l. The corresponding mean concentrations of M6G and M3G were 257 nmol/l and 1943 nmol/l, respectively. Morphine serum trough concentrations showed a 33-fold variation. Seventy percent of the variation was predicted in a model including age, daily morphine dose and M6G/morphine ratio as independent variables. No associations were observed between side effects and serum concentrations of morphine and its metabolites. CONCLUSION: In this study, a mean serum trough morphine concentration of 66 nmol/l was associated with satisfactory pain relief when disease progression required an increase in intensity of pain therapy from step II to step III in the World Health Organization pain ladder. An increased ratio of M6G to morphine serum concentrations predicted lower effective serum morphine concentrations at the time of satisfactory pain relief. This observation supports that M6G contributes to the pain control produced by oral morphine in patients with pain caused by malignant disease.

Antidiuretic hormone levels and the effect of indomethacin on ureteral colic.

We treated 25 patients with ureteral colic and urographically verified stones with 50 mg. indomethacin intravenously. Pain was relieved completely in 17 patients, while in 8 incomplete or no pain relief was achieved after the infusion of indomethacin. Patients completely relieved of pain had significantly higher levels of antidiuretic hormone in plasma before the infusion of indomethacin (18.2 plus or minus 3.4 pg./ml.) than patients with incomplete or no pain relief (7.2 plus or minus 1.3 pg./ml.) (p less than 0.01). These findings indicate that the volume status and/or the level of antidiuretic hormone may be of critical importance for pain relief after infusion of indomethacin in patients with ureteral colic.