Allan Basbaum, PhD

Professor & Chair

The Neurobiological Basis of Pain and Its Control

The development of persistent pain following tissue or nerve injury results to a great extent from profound reorganization of CNS circuits. These changes contribute to a central sensitization/hyperexcitability state that underlies allodynia and hyperalgesia, the hallmarks of persistent pain. Many studies have focused on the injury-induced sprouting of primary afferents and on the physiological properties of altered "pain" transmission neurons in the spinal cord dorsal horn, but there is little information about the tissue and nerve-injury-induced local and long distant circuit changes that occur, in the spinal cord and at more rostral sites.

Our laboratory takes a multidisciplinary approach to the problem, using molecular, pharmacological and behavioral analyses.  Recently, we developed a transgenic mouse in which wheat germ agglutinin transneuronal labeling of complex circuits can be triggered from neurons in any region of the brain or spinal cord, during development or in the adult. We are using these mice to study the development and adult organization of CNS circuits engaged by small diameter primary afferent nociceptors ("pain fibers") and to study their modifications after tissue or nerve injury. Through a highly novel modification of this transneuronal tracing method, in which the tracer is induced in primary afferent neurons only if their peripheral axon has been transected, we are now also able to study nerve injury-induced reorganization of CNS circuits.

Paralleling these studies, we have generated a variety of reporter mice to localize the channels, receptors and transducers through which painful stimuli activate and modulate the nociceptors. Of particular interest are our recent studies demonstrating that the delta opioid receptor is largely associated with sensory neurons with myelinated axons that transmit injury-associated mechanical, rather than thermal (heat) pain sensitivity.

As our objective is to understand the functional significance of the neurochemically distinct nociceptors, our behavioral studies address the consequence of deleting single genes that are enriched in the primary afferent nociceptor, or of deleting populations of nociceptors. Among the genes that we have studied are the V1, A1 and M8 members of the TRP channel family as well as different glutamate transporters. 

Most recently, we have turned out attention to the possibility of overcoming the neurological consequences of peripheral nerve damage, by transplanting embryonic cortical GABAergic precursor cells into the spinal cord, a procedure that we find can ameliorate the persistent pain associated with nerve damage. Taken together, these studies are revealing an entirely new perspective on the circuits that process the injury messages that generate acute and persistent pain and on novel approaches to therapy. 

Lab Members

Joao Braz, Postdoctoral Fellow
Ferda Cevikbas, Postdoctoral Fellow
Todd Dembo, Graduate Student
Alex Etlin, Postdoctoral Fellow
Noemie Frezel, Intern
Zhonghui Guan, Postdoctral Fellow
Dina Juarez-Salinas, Graduate Student
Julia Kuhn, Postdoctoral Fellow

Karuna Meda, Graduate Student
Carlos Solorzano, Postdoctoral Fellow
May Tran, Graduate Student
Smitha Vaman, Research Technician
David Villafuerte, Research Technician
Xidao Wang, Postdoctoral Fellow
Xiaobing Yu, Postdoctoral Fellow 

Lab Website