Cultured human chromaffin cells grafted in spinal subarachnoid space relieves allodynia in a pain rat model

Abstract

Background: Implantation of xenogenic chromaffin cells into the spinal subarachnoid space can produce analgesia in neuropathic pain models. However, transplantation of xenogeneic chromaffin cell has a potential risk of viral or bacterial infections from animals to humans including encephalopathy due to prion transmission. The aim of this study was to investigate the possibility of developing a homogeneic source of therapeutic chromaffin cells.

Methods: Anti-allodynic effects of human chromaffin cells (HCCs) were evaluated in a neuropathic pain model in rats induced by chronic constriction injury of the sciatic nerve. HCCs encapsulated with alginate-poly-L-lysine-alginate were intrathecally implanted into rats (n = 10), while empty capsules were intrathecally implanted as a control (n = 8). Levels of norepinephrine from encapsulated HCCs before and after nicotinic stimulation were measured. We then perfomed a behavior test (cold allodynia) with acetone. In addition, to assess the potential contribution to pain reduction of opioid peptides released from the HCCs, all animals were injected with naloxone.

Results: The concentration of norepinephrine after nicotine stimulation was significantly increased compared to basal levels. Intrathecal implantation of encapsulated HCCs, significantly reduced cold allodynia as compared to rats receiving empty capsules (P < 0.05). Fifteen minutes after the injection of naloxone, cold allodynia significantly decreased in rats with HCCs (P < 0.05), while the degree of cold allodynia in control animals was unaltered.

Conclusions: From these results, it appears that HCCs have a possibility as an analgesic source for transplants delivering pain-reducing neuroactive substances.

Keywords: Analgesics; Chromaffin cells; Pain; Transplants.

Fig. 1

Norepinephrine release from encapsulated human chromaffin cells in vitro. The levels of norepinephrine in Hank's buffered salt solution (HBSS) were evaluated 1, 7, 14, and 30 days after encapsulation by HPLC. ^*P < 0.05 compared with pre-nicotine stimulation.

Fig. 2

Rats developed a cold allodynic response to acetone after ligation of the sciatic nerve. Rats that received microencapsulated human chromaffin cells showed a significant decrease in the withdrawal response to acetone, as compared to the control group (^*P < 0.05). The data are presented as means ± SD. Significant withdrawal time differences between the cell transplantation and control groups were seen (^*P < 0.05 vs Control).

Fig. 3

Effect of naloxone on the degree of cold allodynic response to acetone after nerve ligation in rats with microencapsulated chromaffin cells. ^*P < 0.05 compared to pre-injection of naloxone (2.0 mg/kg, S.C.). The data are presented as means ± SD.