Intrathecal transplantation of neuroblastoma cells decreases heat hyperalgesia and cold allodynia in a rat model of neuropathic pain

Spinal GABAergic Transplants Attenuate Mechanical Allodynia in a Rat Model of Neuropathic Pain

“…To determine whether intraspinally transplanted GABAergic cells could be used in the treatment of allodynia, we used a rat model of neuropathic pain in which L5 and L6 spinal nerve root ligation induced profound and persistent tactile allodynia in the ipsilateral hind paw [77, 83]. Previous studies investigating cell‐based therapies for chronic pain syndromes have deposited cells onto the subarachnoid space [47, , , –51, 55, 56, 59, 60, 61, 84]; however, the reduction of pain behaviors has not been always consistent or sustained [49, 53, 85, 86]. In the present study, we demonstrate that transplantation of GABAergic cells directly into the spinal cord produces a reduction in mechanical allodynia by 1 week post‐transplantation, with peak reductions observed at 4 weeks that persisted even after 6 weeks following transplantation.…”

“…For example, adenosine receptor agonists have been shown to synergistically suppress tactile hypersensitivity in allodynic rats when combined with GABA receptor agonist administration, and administration of both GABA and adenosine receptor antagonists abolished the effects of spinal cord stimulation in abolishing allodynic pain [17, –19]. Transplantation of cells that secrete serotonin [55, –57], galanin [84], or catecholamines or opioid peptides [47, , , , , , –54, 85, 87] have also been shown to significantly improve pain behaviors in animal models of neuropathic pain. Although this effect may have been related to a GABAergic effect by restoration of GABA immunoreactivity to the spinal cord [31, 58], it was also thought to be related to the secretion of non‐GABAergic substances as well.…”

Effect of hydroalcoholic extract of Acorus calamus on tibial and sural nerve transection-induced painful neuropathy in rats

“…Thermal (non-noxious cold) nociceptive threshold, as an index of cold allodynia, was assessed by using the acetone drop method as described by Choi et al [26] with slight modification according to de la Calle et al [27] to assess the reactivity to non-noxious cold chemical stimuli. The rat was placed on the top of the wire mesh grid, allowing access to the hind paws.…”

Review of the History and Current Status of Cell-Transplant Approaches for the Management of Neuropathic Pain

“…Grafts of the mouse B16 F1C29 melanoma cell line, which also release catecholamines, was able to reduce pain behaviors in the tail-flick model when accompanied by morphine [81], but again, such grafts are tumorigenic, and their transplant can itself induce pain behaviors [82]. The monaminergic human NB69 neuroblastoma cell line was able to reduce neuropathic pain in a nerve injury model [83], presumably related to serotonin release from the grafts, but the tumorigenic potential is a consideration with a non-differentiated tumor line. Other studies with implantation of tumor-derived cell lines, like AtT-20 or AtT20/hENK [84], Neuro2A [85], Neuro2A/POMC [86], or P19 [87], that overexpress opioid peptides have been attempted, but such grafts would also carry the risk of tumor formation.…”