We used affinity chromatography to isolate a specific laminin-binding protein from murine fibrosarcoma cells. These cells bind exogenous laminin to their surface with high affinity ( K~ = 2 X 10-9M for laminin) with -5 x 104 sites per cell. Laminin affinity chromatography of [aSS]methioninelabeled cell extracts produced two distinct proteins. One was identified as Type IV (basement membrane) collagen based on its migration pattern on SDS gels and bacterial collagenase sensitivity. The other protein, which migrates as a single band or closely spaced doublet on reduced SDS gels, has a reduced molecular weight of 69,000. Using a nitrocellulose filter disk assay, we found that the latter protein specifically bound 12~l-laminin with the same high affinity ( Kd = 2 X 10-9M for laminin) as did intact fibrosarcoma cells. By iodinating intact cells, we demonstrated that this laminin-binding protein is on the cell surface. We conclude that this protein with reduced molecular weight of 69,000 is a subunit or component of a larger cell surface receptor protein for laminin in this fibrosarcoma model. This laminin receptor may mediate the interaction of the cell with its extracellular matrix.

Many patients with chronic pain have less than optimal therapeutic outcomes after prolonged treatment with opiate analgesics. Worsening of pain perception, functional capacity, and mood often result. Medical detoxification is often undertaken in this situation. Ninety-five consecutive patients (49 men and 46 women; age range, 26-84) with chronic noncancer pain (maldynia) were referred by local pain clinics for detoxification from long-term opiate analgesic (LTOA) therapy. All patients had failed treatment as manifest by increasing pain levels, worsening functional capacity, and, in 8%, the emergence of opiate addiction. Length of prior LTOA therapy ranged from 1.5 to 27 years (mean, 8.8 years). After a minimum of 12 hours of abstinence from all opiate analgesics, patients were given low doses of sublingual (SL) buprenorphine or buprenorphine/naloxone (Reckitt Benckiser). Maintenance dosing was individualized to treat chronic pain. Daily SL dose of buprenorphine ranged from 4 to 16 mg (mean, 8 mg) in divided doses. Mean duration of treatment is 8.8 months (range, 2.4-16.6 months). At clinic appointments, patients were assessed for pain reports, functional capacity, and mood inventory. Eighty-six percent of patients experienced moderate to substantial relief of pain accompanied by both improved mood and functioning. Patient and family satisfaction was robust. Only 6 patients discontinued therapy secondary to side effects and/or exacerbation of pain. In this open-label study, SL buprenorphine and buprenorphine/naloxone were well tolerated and safe and appeared to be effective in the treatment of chronic pain patients refractory to LTOA.

A purified cell surface receptor protein for laminin (Mr = 70,000) isolated from mouse fibrosarcoma cells binds to actin with specificity and high affinity. This binding was demonstrated both by cosedimentation of the receptor with actin and binding of the receptor to actin immobilized on nitrocellulose filters. Specificity was demonstrated by displacement of 'S-labeled receptor by unlabeled receptor. Scatchard analysis of receptor binding to actin yielded a Kd of 6 x 10-7 M. The receptor was observed to reduce the viscosity of actin filaments. It also caused the formation of bundles of parallel filaments. This observation and the stoichiometry of binding suggest that the receptor binds along the sides of actin filaments. Based on the ability of this receptor to bind both extracellular laminin and intracellular actin, we have named this protein "connectin." Connectin may be an example of a transmembrane protein that is capable of mediating the interaction of a cell with its extracellular matrix.

Clinicians are increasingly being challenged by patients who are treated for chronic pain with high-dose opioids that can cause medical, social, and societal harm. These patients may best be improved by psychological approaches, adjuvant medications, and opioid reduction or removal, rather than ever-escalating dosing that has become common. Opioid reduction or removal can be a difficult process that, when done incorrectly, may cause patient dissatisfaction or severe discomfort. Buprenorphine, a partial opioid agonist, is slowly becoming recognized as an effective pain treatment, possessing a wide safety margin while offering the opportunity for stabilization of opioid dosing or even removal. We have developed a protocol for hospitalization of the most fragile or toxic patients detailed herein that can permit a comfortable conversion to buprenorphine from prior high-dose full agonist opioid therapy. Seventy-six consecutive patients with serious medical, psychological, or addiction comorbidities, treated with morphine equivalent doses exceeding hundreds of milligrams per day, were followed after conversion for up to 25 months. Two-thirds reported moderate to dramatic improvements of pain and functional status with an increase seen in employment. Median length of hospital stay was 2 days, and the median daily buprenorphine discharge dose was 8 mg. No adverse reactions or outcomes were observed. A brief hospitalization for conversion from high-dose opioid therapy to a safer, more effective buprenorphine regimen can produce life-altering improvement.

Background and Objectives This study was designed to test whether a brief quantitative sensory testing (QST) assessment could be used to detect hyperalgesia in patients with suspected opioid-induced hyperalgesia. Methods Twenty patients on long-term opioid therapy with suspected opioid-induced hyperalgesia were recruited along with and 20 healthy controls. Pressure pain threshold, Pain50, a measure of intermediate suprathreshold pressure pain sensitivity, and tolerance levels, were evaluated. As a secondary outcome, changes in pressure pain sensitivity following intravenous administration of placebo (saline) and fentanyl (1.5 μg/kg) were assessed. Results There were no significant differences in pain measures between healthy controls and patients. However, there was an association between higher doses of opioids and having a lower pain tolerance (r= -0.46, P=0.041) and lower Pain50 (r=-0.46, P = 0.044), which was consistent with the hypothesis. Patients on >100 mg oral morphine equivalents (OME) displayed decreased pressure pain tolerance compared to patients taking <100 mg OME (P = 0.042). In addition, male patients showed a hyperalgesic response to fentanyl administration, which was significant for the Pain50 measure (P=0.002). Conclusions Whereas there were no differences between patients suspected of having opioid-induced hyperalgesia and the healthy controls, the finding that higher doses of opioids were associated with more sensitivity suggests that dose might be an important factor in the development of hyperalgesia. In addition, male patients demonstrated a hyperalgesic response after a bolus of fentanyl. Future studies are needed to develop better diagnostics for detecting hyperalgesia in the clinical setting.