F A C U L T Y P R O F I L E
SCHOLZ, JOACHIM, M.D.
Cellular and molecular mechanisms of chronic pain.
Office: Black Building | Room 1111
Pain serves an important protective function: it is a physiological response to harmful environmental or internal stimuli that alerts us of imminent tissue damage. However, in the presence of inflammation or repeated injury, pain no longer accurately reflects the nature or intensity of these stimuli. The sensation of pain increases and spreads beyond the injury site. Pain may even occur spontaneously, in the absence of a recognizable stimulus. Chronic back pain and pain associated with osteoarthritis are clinical examples of such inflammatory pain.
Neuropathic pain develops after a lesion or disease that directly affects the nervous system. Neuropathic pain has long been considered an exclusively neuronal “affair”. However, it is now clear that nerve lesions, too, provoke a marked inflammatory response that involves circulating and resident immune cells in the periphery and glial cell populations in the central nervous system. My laboratory is interested in identifying the molecular messages that neurons, immune cells and glia exchange with each other. We want to determine the signals that trigger recruitment and activation of immune and glial cells, and examine how signals released from immune and glial cells alter neuronal activity.
A key relay station for somatosensory information including pain is the dorsal horn of the spinal cord. Here, local interneurons and descending pathways from the brain jointly control the processing of afferent input. Nerve injury disrupts these control mechanisms profoundly. Using persistent neuropathic pain as a model of maladaptation in the nervous system, we study the impact of peripheral nerve lesions on the balance between excitatory and inhibitory regulation of synaptic transmission in the dorsal horn and the consequences for neuronal survival and function.
In an exciting new avenue of research, we are using stem cell technology to examine intrinsic risk factors for neurodegeneration and pain in diabetic neuropathy. The central idea behind this approach is to develop a model of neuropathy based on human induced pluripotent stem cells (iPSCs) that we derive from patients with type 2 diabetes. To generate neurons from iPSCs, we collaborate with colleagues in the Stem Cell Initiative at Columbia University and the Harvard Stem Cell Institute. Planned and ongoing research includes the functional analysis of these neurons, the exploration of mechanisms responsible for peripheral neurodegeneration and pain, and the identification of potential targets for therapeutic intervention.
1. Scholz J, Yaksh TL. Preclinical research on persistent postsurgical pain: what we don't know, but should start studying. Anesthesiology 2010; 112(3):511–3.
2. Scholz J, Mannion RJ, Hord ED, Griffin RS, Rawal B, Zheng H, Scoffings D, Phillips A, Guo J, Laing RJC, Abdi S, Decosterd I, Woolf CJ. A novel tool for the assessment of pain: validation in low back pain. PLoS Med 2009; 6(4):e1000047.
3. Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 2009; 32:1–32.
4. Scholz J, Abele A, Marian C, Häussler A, Herbert TA, Woolf CJ, Tegeder I. Low-dose methotrexate reduces peripheral nerve injury-evoked spinal microglial activation and neuropathic pain behavior in rats. Pain 2008; 138(1):130–142.
5. Griffin RS, Costigan M, Brenner GJ, Ma CHE, Scholz J, Moss A, Allchorne AJ, Stahl GL, Woolf CJ. Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. J Neurosci 2007; 27(32):8699–708.
6. Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells, and glia. Nat Neurosci 2007; 10(11):1361–8.
7. Tegeder I, Costigan M, Griffin RS, Abele A, Belfer I, Schmidt H, Ehnert C, Nejim J, Marian C, Scholz J, Wu T, Allchorne A, Diatchenko L, Binshtok A, Goldman D, Adolph J, Sama S, Atlas SJ, Carlezon WA, Parsegian A, Lötsch J, Fillingim RB, Maixner W, Geisslinger G, Max MB, Woolf CJ. GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 2006; 12(11):1269–77.
8. Scholz J, Broom DC, Youn DH, Mills CD, Kohno T, Suter MR, Moore KA, Decosterd I, Coggeshall RE, Woolf CJ. Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury. J Neurosci 2005; 25(32):7317–23.
9. Benn SC, Perrelet D, Kato AC, Scholz J, Decosterd I, Mannion, RJ, Bakowska JC, Woolf, CJ. Hsp27 upregulation and phosphorylation is required for injured sensory and motor neuron survival. Neuron 2002; 36(1):45–56.
10. Moore KA, Kohno T, Karchewski L, Scholz J, Allchorne A, Baba H, Woolf CJ. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci 2002; 22(15):6724–31.
11. Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci 2002; 5 (Suppl):1062–7.