Data from: Pain persists in mice lacking both Substance P and CGRPα signaling

The neuropeptides Substance P and CGRPα have long been thought important
for pain sensation. Both peptides and their receptors are expressed at
high levels in pain-responsive neurons from the periphery to the brain
making them attractive therapeutic targets. However, drugs targeting these
pathways individually did not relieve pain in clinical trials. Since
Substance P and CGRPα are extensively co-expressed we hypothesized that
their simultaneous inhibition would be required for effective analgesia.
We therefore generated Tac1 and Calca double
knockout (DKO) mice and assessed their behavior using a wide range of
pain-relevant assays. As expected, Substance P and CGRPα peptides were
undetectable throughout the nervous system of DKO mice. To our surprise,
these animals displayed largely intact responses to mechanical, thermal,
chemical, and visceral pain stimuli, as well as itch. Moreover, chronic
inflammatory pain and neurogenic inflammation were unaffected by loss of
the two peptides. Finally, neuropathic pain evoked by nerve injury or
chemotherapy treatment was also preserved in peptide-deficient mice. Thus,
our results demonstrate that even in combination, Substance P and CGRPα
are not required for the transmission of acute and chronic pain.