scholarly journals Patrick David Wall. 5 April 1925—8 August 2001

Author(s):  
Maria Fitzgerald

Patrick (Pat) Wall was a neurophysiologist and true pioneer in the science of pain. He discovered that the sensory information arising from receptors in our body, such as those for touch and heat, could be modified, or ‘gated’, in the spinal cord by other sensory inputs and also by information descending from the brain; this meant, as is now well recognized, that the final sensory experience is not necessarily predictable from the original pain-eliciting sensory input. He used this to explain the poor relationship between injury and pain, and to illustrate the fallacy of judging what someone ‘should’ be feeling from the sensory input alone. In 1969, together with his colleague, Ron Melzack, Pat proposed the ‘gate control theory of pain’ and the circuit diagram that summarized how central spinal cord circuits can modulate sensory inputs. Later on, he began to regret that ‘goddamned diagram’, which had come to dominate his life and work, but, like all great models, it paved the way for the future. Now, over 50 years after it was first published, molecular genetic dissection of dorsal horn neuronal circuitry has indisputably confirmed that sensory inputs are indeed ‘gated’ in the spinal cord dorsal horn. Through a career that started with a medical degree in Oxford, followed by almost 20 years at Yale and MIT in the USA, and continued at University College London, Pat Wall was a highly influential, critical, creative and original thinker who revolutionized our understanding of the relationship between injury and pain, and who also became a champion for all who suffered from chronic pain.

2021 ◽  
Vol 22 (1) ◽  
pp. 414
Author(s):  
Antonella Comitato ◽  
Rita Bardoni

Sensory primary afferent fibers, conveying touch, pain, itch, and proprioception, synapse onto spinal cord dorsal horn neurons. Primary afferent central terminals express a wide variety of receptors that modulate glutamate and peptide release. Regulation of the amount and timing of neurotransmitter release critically affects the integration of postsynaptic responses and the coding of sensory information. The role of GABA (γ-aminobutyric acid) receptors expressed on afferent central terminals is particularly important in sensory processing, both in physiological conditions and in sensitized states induced by chronic pain. During the last decade, techniques of opto- and chemogenetic stimulation and neuronal selective labeling have provided interesting insights on this topic. This review focused on the recent advances about the modulatory effects of presynaptic GABAergic receptors in spinal cord dorsal horn and the neural circuits involved in these mechanisms.


Neuron ◽  
2014 ◽  
Vol 81 (6) ◽  
pp. 1443 ◽  
Author(s):  
Rita Bardoni ◽  
Vivianne L. Tawfik ◽  
Dong Wang ◽  
Amaury François ◽  
Carlos Solorzano ◽  
...  

2001 ◽  
Vol 435 (3) ◽  
pp. 276-282 ◽  
Author(s):  
Richard E. Coggeshall ◽  
Helena A. Lekan ◽  
Fletcher A. White ◽  
Clifford J. Woolf

2008 ◽  
Vol 109 (5) ◽  
pp. 879-889 ◽  
Author(s):  
Dae-Hyun Roh ◽  
Hyun-Woo Kim ◽  
Seo-Yeon Yoon ◽  
Hyoung-Sig Seo ◽  
Young-Bae Kwon ◽  
...  

Background Selective blockade of spinal sigma(1) receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain. Methods Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. The Sig-1R antagonist BD1047 was administered intrathecally twice daily from postoperative days 0 to 5 (induction phase of neuropathic pain) or from days 15 to 20 (maintenance phase). Western blot and immunohistochemistry were performed to determine changes in Sig-1R expression and to examine the effect of BD1047 on N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation in spinal cord dorsal horn from neuropathic rats. Results BD1047 administered on postoperative days 0-5 significantly attenuated CCI-induced mechanical allodynia, but not thermal hyperalgesia, and this suppression was blocked by intrathecal administration of the Sig-1R agonist PRE084. In contrast, BD1047 treatment during the maintenance phase of neuropathic pain had no effect on mechanical allodynia. Sig-1R expression significantly increased in the ipsilateral spinal cord dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30 nmol) administered intrathecally during the induction, but not the maintenance phase, blocked the CCI-induced increase in N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation. Conclusions These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.


Sign in / Sign up

Export Citation Format

Share Document