Understanding the precise molecular mechanisms behind chronic pain disorders such as migraine and opioid induced hyperalgesia (OIH) has been a long-standing goal met with limited success. Neuropeptides, which play a vital role in several physiological processes are also hypothesized to be involved in mediating these pain mechanisms. Here we show that change in levels of several neuropeptides and neuropeptide-precursor proteins (prohormones) correlate with migraine and OIH in mice. We also identified common prohormones that are significantly changed in both migraine and OIH. These results suggest that neuropeptides have an important role in these chronic pain disorders and might be key towards unlocking their mechanisms. This knowledge could eventually be utilized in developing an effective cure for these disorders.