In 2012, we published the first special issue on mechanisms of pain and itch in Neuroscience Bulletin, which covered the peripheral, central, and glial mechanisms of pain and itch [1–5]. In the last 5 years, the field has seen tremendous progress in the molecular and functional characterization of primary sensory neurons [6, 7], neurocircuits of pain and itch [8–10], immune and glial modulation of pain and itch [11–15], molecular mechanisms of pain [16, 17], and identification of brain signatures of pain [18]. Thus, it is timely to highlight the recent progress in a second special issue. I invited the previous authors and new authors from China, the USA, and Japan, and they have contributed 20 mini-reviews and original articles to this special issue. Primary sensory neurons of the dorsal root ganglion (DRG) consist of pain-sensing nociceptive neurons and itch-sensing pruriceptive neurons. Significant progress has been made in the molecular and functional characterization of these sensory neurons, thanks to the development of novel techniques and approaches [6, 7]. Using a combination of functional characterization and high-coverage single-cell RNA sequencing, Zhang and colleagues identified 11 types of somatosensory neurons [19]. In addition to single-cell analysis, Dong and coworkers investigated sensory neuron activation and pain mechanisms using Ca2+ imaging in intact animals following various sensory stimuli. They also discuss the advantages and potential methodological considerations of GCaMP imaging [20]. Sodium channels play a critical role in the pathogenesis of pain and itch. For example, the TTX-resistant Na+ channel subunit Nav1. 8 contributes to the development of bone cancer pain in rodents [16]. To enhance the translational potential of preclinical studies, Chang et al. compared the expression of TTX-sensitive and TTX-resistant Na+ channel subtypes in mouse and human DRG neurons and demonstrated striking species differences: the human DRG has much higher expression of the Nav1. 7 subtype and lower expression of Nav1. 8, whereas the mouse DRG has higher expression of Nav1. 8 but lower expression of Nav1. 7. The authors also established a translational model in which to study ‘‘human pain in a dish’’, induced by the chemotherapeutic drug paclitaxel [21]. Human genetic study revealed a critical role of Nav1. 7 (SCN9A) in human pain perception, but specific targeting of Nav1. 7 has been a challenge. Bang et al. tested a monoclonal antibody that targets the voltage sensor of Nav1. 7 (SVmab) and showed that it selectively inhibits Nav1. 7 but not other Na+ channel subtypes in HEK293 cells. They also showed that SVmab inhibits Na+ currents in native sensory neurons and reduces neuropathic pain in mice. Furthermore, they revealed different activities of hybridoma-derived and recombinant SVmab, which will lead to new strategies for therapeutic development [22]. Latremoliere and Costigan discuss how a combination of human and mouse genetics helps to identify new pain targets and analgesics. Using an approach of reverse translation (from human to mouse), they have identified tetrahydrobiopterin (BH4) as a novel pathway for pathological pain, as well as new compounds that can block this pathway for pain relief [23]. It is noteworthy that pain and itch often accompany infections caused by viral, bacterial, parasitic, and fungal