UNASSIGNED: @entity9 induced by @entity1566 ( @entity1566 ) is clinically challenging with inadequate long-term treatment options. Partial @entity158 relief offered by pharmacologic treatment is often counterbalanced by adverse effects after prolonged use in @entity1118 @entity1 . Cell-based therapy for @entity9 using GABAergic neuronal progenitor cells (NPC) has the potential to overcome untoward effects of systemic pharmacotherapy while enhancing analgesic potency due to local activation of GABAergic signaling in the spinal cord. However, @entity154 underlying @entity1118 will likely require simultaneous targeting of multiple mechanisms. Here we explore the analgesic potential of genetically modified @entity35 embryonic GABAergic NPCs releasing a peptidergic @entity3391 receptor antagonist, @entity563 -histogranin (SHG), thus targeting both spinal hyperexcitability and reduced inhibitory processes. Recombinant NPCs were designed using either lentiviral or adeno-associated-viral vectors ( @entity4700 /8) encoding single and multimeric (6 copies of SHG) cDNA. Intraspinal injection of recombinant cells elicited enhanced analgesic effects compared to nonrecombinant NPCs in @entity1566 -induced @entity158 in @entity35 . Moreover, potent and sustained antinociception was achieved, even following a 5 weeks post-injury delay, using recombinant multimeric NPCs. Intrathecal injection of SHG antibody attenuated analgesic effects of the recombinant grafts suggesting active participation of SHG in these antinociceptive effects. Immunoblots and immunocytochemical assays indicated ongoing recombinant peptide production and secretion in the grafted host spinal cords. These results support the potential for engineered NPCs grafted into the spinal dorsal horn to alleviate chronic @entity9 .

Recombinant neural progenitor transplants in the spinal dorsal horn alleviate chronic central XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity154 :: ('MESH:D000013', 'Disease') :: ['multifactorial anomalies'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity3391 :: ('D016202', 'Chemical') :: ['NMDA'] @entity4700 :: ('10804', 'Species') :: ['AAV2'] @entity158 :: ('MESH:D010146', 'Disease') :: ['pain'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['Serine'] @entity1566 :: ('MESH:D013119', 'Disease') :: ['spinal cord injury', 'SCI'] @entity1118 :: ('MESH:D059350', 'Disease') :: ['chronic pain'] @entity9 :: ('MESH:D009437', 'Disease') :: ['neuropathic pain', 'Neuropathic pain']
@entity9 :: (MESH:D009437,Disease) :: ['neuropathic pain']
