Microencapsulated Bovine Adrenal Medullary Chromaffin Cells Transplanted into Rat Spinal Cord Alleviated Cold Allodynia / 대한마취과학회지

BACKGROUND: The intrathecal grafting of adrenal chromaffin cells as a potential analgesic source, to delivery analgesic substances such as catecholamines and opioid peptides, is known to be effective at treating acute and chronic pain in several animal pain models. We tested whether the intrathecal implantation of encapsulated bovine chromaffin cells reduces cold allodynia in a rat model of neuropathic pain induced by chronic constriction injury of the sciatic nerve. METHODS: Bovine adrenal medullary chromaffin cells microencapsulated in sodium alginate-poly-l-lysin-alginate (APA) were implanted into the subarachnoid space of rats (n = 10) and foot cold sensitivity was investigated using an acetone test. At the end of the study, histology and capsule catecholamine production were evaluated. RESULTS: A significant reduction in cold allodynia was observed in animals implanted with chromaffin cells. In addition, the suppression of cold allodynia was reversed by naloxone. Abundant clusters of viable chromaffin cells stained with neutral red, were observed in the retrieved implants and after nicotine stimulation, and catecholamine was quantified. An ultrastructural study showed no fibrotic reaction against capsules, or disorganised capsules. CONCLUSIONS: These results suggest that intrathecal encapsulated chromaffin cells act as "mini pumps", which continuously deliver analgesic substances and produce analgesia in this chronic pain model of nerve injury-without immunosuppressant.

Do Microencapsulated Bovine Adrenal Medullary Chromaffin Cells Transplanted in Rats' Spinal Cord Produce Analgesic Effects? / 대한마취과학회지

BACKGROUND: Pain remains the chief complaint that brings patients to physician's office, despite recent insights into underlying mechanism and the identification of potential new therapeutic targets. In recent years, however, with the development of molecular biology cell transplantation gives us a new chance for treating intractable chronic pain. The major purpose of the present study was to determine if the chromaffin cells that were encapsulated with 1.3% (w/v) sodium alginate-poly-l-lysine-alginate (APA) had robust analgesic effects in the spinal atlanto-occipital subarachnoid space even without nicotine stimulation. METHODS: In order to determine whether microencapsulated bovine adrenal medullary chromaffin cells transplanted in the spinal cord can produce analgesic effects, we microencapsulated adrenal medullary chromaffin cells with APA and implanted them into the subarachnoid space of rats' (n = 10) spinal cord, and investigated the hot sensitivity of rats' hind-paw by a light-beam test. RESULTS: It was found that compared with the control group, hot response latency of the group which received adrenal medullary chromaffin cells increased from the 12th day and the analgesic efficacy was maintained for at least 75 days. CONCLUSIONS: Microencapsulated bovine adrenal medullary chromaffin cells transplanted in the rats' spinal cord may provide a permanent and locally available source of neuropeptides for the relief of intractable pain. Furthermore, these kinds of analgesic effect were produced without any stimulation such as nicotine.

The Regulation of AP-1 DNA Binding Activity by Long-term Nicotine Stimulation in Bovine Adrenal Medullary Chromaffin Cells: Role of Second Messengers

The signal pathways involved in the regulation of AP-1 DNA binding activity in long-term nicotine stimulated bovine adrenal medullary chromaffin (BAMC) cells have not been well characterized. To understand the involvement of second messengers in the regulation of AP-1 DNA binding activity, the present study was designed to define the time-course for inhibition of nicotine-induced responses by cholinergic antagonists, Ca2+ and calmodulin (CaM) antagonists, and calcium/calmodulin-dependent protein kinase (CaMK) II inhibitor using electrophoretic mobility shift assay. Nicotine (10microM) stimulation increased AP-1 DNA binding activity at 24 hr after treatment. Posttreatment with hexamethonium (1 mM) plus atropine (1microM) (HA), nimodipine (1microM), or calmidazolium (1microM) at 0.5, 3, and 6 hr after the nicotine treatment significantly inhibited the AP-1 DNA binding activity increased by long-term nicotine stimulation. However, posttreatment with HA, nimodipine, or calmidazolium at 9 or 12 hr after the nicotine treatment did not affect the nicotine-induced increase of AP-1 DNA binding activity. The pretreatment of BAMC cells with various concentrations of KN-62 inhibited the increase of AP-1 DNA binding activity induced by nicotine in a concentration-dependent manner. KN-62 (10microM) posttreatment beginning at 0.5, 3, or 6 hr after the nicotine treatment significantly inhibited the increase of AP-1 DNA binding activity. However, KN-62 posttreatment beginning at 9 or 12 hr after the nicotine treatment did not affect the increase of AP-1 DNA binding activity. This study suggested that stimulation (for at least 6 hr) of nicotinic receptors on BAMC cells was necessary for increase of AP-1 DNA binding activity, and activation of Ca2+, CaM, and CaMK II up to 6 hr at least seemed to be required for the increase of nicotine-induced AP-1 DNA binding activity.

Analgesic Effect of Transplanted Adrenal Medullary Chromaffin Cells in Rats Spinal Cord / 대한마취과학회지

BACKGROUND: Despite of numerous researches on the mechanisms and new therapeutic methods of chronic pain, patients are still suffering even with the help of opioids. In recent years, however, with the development of molecular-biology cell transplantation gives us a new chance for treating intractable chronic pain. The major purpose of the present study was to determine if the chromaffin cells have robust analgesic effects in the spinal atlanto-occipital subarachnoid space even without nicotine stimulation. METHODS: In order to determine whether cultured bovine adrenal medullary chromaffin cells transplanted in the spinal cord can produce analgesic effects, we purified adrenal medullary chromaffin cells and implanted them into the subarachnoid space of rats' (n = 10) spinal cord without immunosuppression, and investigated the hot sensitivity of rats' hind-paw by a light-beam test. RESULTS: It was found that compared with the control group, hot response latency of the group which received adrenal medullary chromaffin cells had increased at 14 days and the analgesic efficacy was maintained for at least 3 months. CONCLUSIONS: Adrenal medullary chromaffin cells transplanted in the rats' spinal cord may provide a permanent and locally available source of neuropeptides for the relief of intractable pain. Furthermore, these kinds of analgesic effect even produced without any stimulation such as nicotine.