Goran Pandev struck twice for the hosts but Pepe popped up with the goal that salvaged a point after a barnstorming run as Juve piled on the pressure to stretch their lead over AC Milan to two points after 12 games with Napoli up to sixth on 17.
Marek Hamsik, having missed an early penalty, headed the home side in front midway through the first half before Pandev doubled their lead just before the break.
Bianconeri boss Antonio Conte praised his side's "inner strength" when they were behind.
"Without heart, you don't come back in games like these," he told Italy's Sky Sport channel. "We were a bit soft in the first half but the boys showed they wanted it tonight."
"I view the glass as half empty not half full with this result," he told Sky Sport.
"It was a spectacular first half but we collapsed after the break because we're playing twice a week and just didn't have the energy that they had to pressurise at the end."
But it was the home side, backed by loud support from another full house in the capital of Italy's south, who were gifted the chance to break the deadlock seven minutes later when Andrea Pirlo brought down Ezequiel Lavezzi inside the box.
The controversial moment appeared to fire Napoli up and they took the lead after 22 minutes when Lavezzi's free-kick fell to Hamsik on the edge of the six-yard box and the midfielder made no mistake with a diving header.
Juve keeper Gianluigi Buffon had to be at full stretch to save the Macedonian's low skidding shot from the edge of the box after 26 minutes before the striker shanked his near-post effort wide after superb approach play from Lavezzi.
Five minutes before half-time the dangerous Pandev got his reward, latching onto a another ricochet inside the area before applying a low finish across Buffon's to put Napoli 2-0 ahead.
But Napoli restored their two-goal lead after 68 minutes when Pandev controlled Christian Maggio's difficult cross before swivelling to brilliantly volley the ball in off the post.
Five minutes later, though, Maggio went missing in defence allowing Estigarribia plenty of time to control Matri's cross and poke the ball under the diving Morgan De Sanctis for the Paraguayan's first goal in Italian football.
